Principles of
BIOCHEMISTRY
Dr. AHMED KHAMIS MOHAMED SALAMA
Medical Laboratories Dept., Colleges compound at Zulfi
February 2013
1
Introduction to Biochemistry
The cell is the basic unit of living organisms. The basic components
of animal cell are indicated as:
1. Plasma membrane: Surrounds the cell as a selectively
permeable membrane.
2. Cytoplasm: Composed mostly of water.
3. Nucleus: Contains genetic information, or instructions for
making molecules (DNA).
4. Ribosome: Produces proteins.
5. Lysosome: Contains enzymes that digests wastes.
6. Mitochondrion: Breaks down glucose with oxygen to produce
energy.
7. Endoplasmic reticulum: Transports materials throughout the
cell.
2
Basic Biochemistry Terms
Living systems are composed of very complex molecules (polymers)
which built from many small molecules. These small molecules are
called monomers and are the basic unit of these polymers. Different
kinds
and
sequences
of
monomers
come
together to
form
compounds with different characteristics.
Monomers come together by a process called dehydration synthesis.
A hydrogen atom from one functional group joins together with a
hydroxide ion from a functional group of another molecule, which
results in water and a bond formed between the two molecules. This
is called dehydration synthesis. Hydrolysis is just the opposite.
3
Amino acid
Amino acids (the monomers of proteins) coming together
to make dipeptide.
4
Polarity is very important and plays an important role in cell
membranes. You should remember that like dissolves like. Polar
molecules will always dissolve in water, while non-polar ones will
not. Substances that are attracted to water are called hydrophilic
and ones that are not are called hydrophobic.
Biomolecules in the living organism:
1. Carbohydrates
Carbohydrates are the major energy source for living organisms.
Mitochondria break down carbohydrates and use the chemical
energy released from its bonds to live. Carbohydrates always have a
1:2:1 ratio of carbon, hydrogen, and oxygen. Since the empirical
formula is CH2O, they are called carbohydrates.
The monomers of carbohydrates are called monosaccharides and are
also called simple sugars. Some popular monosaccharides are
glucose, fructose, ribose, and galactose. Oligosaccharides are
composed of 2-8 monomers (sucrose, lactose, maltose) . However,
some very important carbohydrates are composed of thousands of
monomers
and
are
called
polysaccharides
(starch,
cellulose,
glycogen).
2. Proteins
Proteins provide structure, and organic catalysts are mostly made of
proteins. They can also be used to store energy. They are produced
by ribosome in our cells.
Fibrous proteins provide structure and are usually long and thin.
Examples include muscles, hair, cartilage, veins, ducts, and other
structures.
Globular proteins do things other than structure, like transport
oxygen and nutrients, fight invasions by foreign objects, help
5
maintain homeostasis in the body (hormones), and catalyze
reactions that would take too long in their absence (enzymes).
Conjugated proteins do various functions throughout the body. It
means that proteins connected to a non-protein moiety such as a
sugar
(glycoproteins),
nucleic
acid
(nucleoproteins),
lipid
(lipoproteins).
Amino Acids:
They are the monomers of proteins. The basic
parts of an amino acid are an amine group, a carboxylic group, and a
side chain, all attached to an alpha-carbon (central carbon).
The bond between two amino acids is called a peptide bond.
There are only 20 R-groups, and therefore only 20 kinds of amino
acids found in nature, 8 of which that can be produced by humans
and called non-essential amino acids. The rest we have to obtain by
eating stuff, and these are called essential amino acids. Surprisingly,
the number of combinations of amino acids is almost endless.
6
3. Lipids
Lipids are also very important to structure. Lipids and conjugated
compounds
include
fats,
oils,
phospholipids,
waxes,
terpens,
steroids.
A common fat is composed of glycerol and long chains of carboxylic
acids called fatty acids. They are generally referred to as
triglycerides. Triglycerides can be decomposed by adding NaOH.
Fatty acids are saturated if there are no double bonds in their chain,
unsaturated if there is one double bond, and polyunsaturated if
there is more than one double bond.
Saturated fatty acids tend to be solid, since they form straight lines
and can stack on top of each other. On the other hand, unsaturated
fats are liquid at room temperature because since they have a
double bond, their shape is bent and they can't form layers as well.
7
Phospholipids are similar to triglycerides, only the phospholipid has
two fatty acid tails and one phosphate group. Our cell membranes
are composed of phospholipid bilayers through which small
molecules like water and air can diffuse through.
Unlike triglycerides and phospholipids, waxes contain monohydroxy
alcohols instead of glycerol (which has three hydroxyl groups). They
are solids with low melting points, and are used as waterproof both
in nature and commercially.
Some important steroids
1. Cholesterol: It is the most widespread animal steroid and is
found in almost all animal tissues.
Cholesterol is a necessary
intermediate in the biosynthesis of the steroid hormones; however,
since it can be synthesized from acetylcoenzyme-A CH3CO- Co-A , it
is not a dietary necessity. High levels of blood cholesterol hardening
of the arteries.
2. Cortisone and cortisol
These hydrocortisone hormones secreted by the adrenal cortex.
They are widely used to treat inflammation due to allergies or
rheumatoid arthritis.
3. Sex hormones
8
They are produced primarily in the testes or the ovaries; their
production is regulated by pituitary hormones. Male hormones are
collectively called androgens; female hormones, estrogens; and
pregnancy hormones, progestins.
4. Bile acids
They are found in bile, which is produced in the liver and stored in
the gall bladder. The structure of cholic acid, the most abundant
bile acid, follows. Bile acids are secreted into the intestines to keep
lipids emulsified in the intestines, thereby promoting their digestion.
4. Nucleic Acids
In order for life to go on for generations, organisms need to transmit
genetic material to the next generation. Somehow this information
needs to be stored somewhere, and be easy to duplicate during
reproduction. DNA and RNA have the perfect structure for governing
the cell (telling it what molecules to make and how) and are
practical to duplicate.
9
Nucleotides: are the monomers of nucleic acids. They are made up
of three parts: a five-carbon sugar, a nitrogenous base, and a
phosphate group:
10
11
1. CARBOHYDRATES
Carbohydrates are the most abundant class of biomolecules found in
living organisms. They originate as products of photosynthesis, an
endothermic reductive condensation of carbon dioxide requiring
light energy and the pigment chlorophyll.
12
Carbohydrates fill numerous roles in living things, such as:

Carbohydrates are the major source of metabolic energy
(storage and transport of energy, starch, glycogen).

Carbohydrates serve as a structural components (cellulose in
plants, chitin in animals).

Carbohydrates are one of the three essential components of
DNA and RNA.

Carbohydrates and their derivatives play major roles in the
working process of the immune system, pathogenesis, blood
clotting, and development.
The formulas of many carbohydrates can be written as carbon
hydrates, Cn(H2O)n.
Many carbohydrates have the empirical formula CH2O; for example,
the molecular formula for glucose is C6H12O6 (six times CH2O). So
carbohydrates are
naturally
occurring compounds of carbon,
hydrogen, and oxygen.
13
Carbohydrates are actually polyhydroxy aldehydes and ketones or
their derivatives.
The carbohydrates vary dramatically in their properties.
For
example, sucrose (table sugar) and cellulose (plant) are both
carbohydrates.
One of the principal differences between various
types of carbohydrates is the size of the molecules.
The monosaccharides (often called simple sugars) are the simplest
carbohydrate
units;
they
cannot
be
hydrolyzed
to
smaller
carbohydrate molecules. Monosaccharides can bonded together to
form dimmer, trimer, etc. and, ultimately, polymers. The dimmers
are called disaccharides.
Sucrose is a disaccharide that can be
hydrolyzed to one unit of glucose plus one unit of fructose.
The monosaccharides and disaccharides are soluble in water and are
generally sweet-tasting.
14
15
The names of carbohydrates often end in the suffix -ose.
Carbohydrates composed of 2 – 8 units of monosaccharides are
referred to as oligosaccharides.
If more than 8 units
of
monosaccharides result from hydrolysis, the carbohydrate is a
polysaccharide.
Example of polysaccharides are:

starch, found in flour and cornstarch.

Cellulose, a fibrous constituent of plants and the principal
component of cotton.
16
The following figure shows dimentional formulas and Fischer
projections for monosaccharides.
17
Fischer projections:
Emil Fischer introduced projection formulas for showing the spatial
arrangement of groups around chiral carbon atoms.
Dimensional formula of the chain
The Fischer projection of the chain
form of D-glucose
form of D-glucose
18
Fischer projection is simply a shorthand way to represent a ball –
and – stick or dimensional formula. In drawing a Fischer projection,
we assume that the molecule is completely stretched out in the
plane of the paper with all its substituent. Each intersection of the
horizontal and vertical lines represents a chiral carbon atom. Each
horizontal line represents a bond coming toward the viewer, while
the vertical line represents bonds going back, away from the viewer.
A pair of enantiomers of pentose is easily recognized when Fischer
projections are used.
Mirror image
19
Fischer projections
Emil Fischer introduced projection formulas for showing the spatial
arrangement of groups around chiral carbon atoms.
Nomenclature
Aldoses such as glucose (six carbon atoms) are named aldohexose,
ripose (five carbon atoms) are named aldopentose and so on.
Ketoses such as fructose (six carbon atoms) are named hexulose,
xylose (five carbon atoms) are named pentulose and so on.
20
Aldose
Aldotriose
D-Glyceraldehyde
Aldotetroses
D-Erythrose
D-Threose
21
Aldopentoses
D-Ribose
D-Arabinose
D-Xylose
D-Lyxose
Aldohexoses
D-Allose
D-Altrose
D-Glucose
D-Mannose
22
D-Gulose
D-Idose
D-Galactose
D-Talose
Ketoses
Triulose
Dihydroxyacetone
Tetrulose
D-Erythrulose
23
Pentulose
D-Ribulose
D-Xylulose
Hexulose
D-Psicose
D-Fructose
24
D-Sorbose
D-Tagatose
SOME MONOSACCHARIDES
Glucose:
Glucose
is the most important of the monosaccharides, is sometimes
called blood sugar (because it is found in the blood), grape sugar
(because
it
is
found
in
grapes),
or
dextrose
(because
it
is
dextrorotatory). Mammals can convert sucrose, lactose (milk sugar),
maltose, and starch to glucose, which is then used by the organism for
energy or stored as glycogen (a polysaccharide).
When the organism needs energy, the glycogen is again converted to
glucose. Excess carbohydrates can be converted to fat; therefore a
person can become obese on a fat-free diet. Carbohydrates can also be
converted to steroids (such as cholesterol) and, to a limited extent, to
protein.
Conversely, an organism can convert proteins and fats to
carbohydrates.
25
Fructose:
Fructose is ketosugars, have sex carbon atoms, named hexulose. It is
also called levulose because it is levorotatory.
Fructose is the sweetest-tasting of all the sugars. It occurs in fruit and
honey, as well as in sucrose.
26
Galactose
Galactose is aldosugars, have sex carbon atoms,
aldohexoses. It is found in milk as
it is named
bonded to glucose, in the
disaccharide lactose.
Ribose and deoxyribose
Ribose is form part of the polymeric backbone of the nucleic acid RNA
while deoxyribose is form part of the polymeric backbone of the nucleic
acid DNA. The prefix deoxy- means “ minus an oxygen”; the structures
of ribose and deoxyribose are the same except that deoxyribose lacks
an oxygen at carbon 2.
27
Classification of monosaccharides
Monosaccharides are classified according to:
1. The placement of its carbonyl group
If the carbonyl group is an aldehyde, the monosaccharide is an aldose;
if the carbonyl group is a ketone, the monosaccharide is a ketose.
Examples for aldoses: glucose, galactose, ribose, and deoxyribose.
Examples for ketoses: fructose
28
2. The number of carbon atoms it contains (usually from 3-7 atoms)
Monosaccharides with three carbon atoms are called trioses, those
with four are called tetroses, five are called pentoses, six are hexoses,
and so on.
These two systems of classification are often combined. For example,
glucose is an aldohexose (a six-carbon aldehyde), ribose is an
aldopentose (a five-carbon aldehyde), and fructose is a ketohexose (a
six-carbon ketone).
3. Its optical isomers.
Each carbon atom bearing a hydroxyl group (-OH) are asymmetric,
making them stereo-centers.
The assignment of D or L is made according to the orientation of the
asymmetric carbon furthest from the carbonyl group: in a standard
Fischer projection if the hydroxyl group is on the right the molecule is a
D sugar, otherwise it is an L sugar.
Because D sugars are biologically far more common, the D is often
omitted.
29
Configuration of Glucose
Glucose has six carbon atoms, four of which are chiral centers (Carbons
2,3,4, and 5)
indicate there may be as many as
sixteen (24)
stereoisomers.
Only half of these sixteen sterioisomers belong to the D-series; of
these,
only
D-glucose,
D-galactose,
and
D-mannose
occur
in
abundance.
The Fisher projection of all the D-aldoses, from D-glyceraldehyde
through the D-aldohexoses, are shown below.
The addition of one more carbon creates a new chiral carbon in each
step down in the figure. Therefore, D-glyceraldehyde leads to a pair of
30
tetroses, each tetrose leads to a pair of pentoses and each pentose
leads to a pair of hexoses.
31
Ketoses
32
33
Cyclization of Monosaccharides
The preferred structural form of many monosaccharides may be that of
a cyclic hemiacetal.
A general reaction of alcohols and aldehydes is that of hemiacetal
formation
Five and six-membered rings are favored over other ring sizes because
of their low angle and eclipsing strain. Cyclic structures of this kind are
termed
furanose
(five-membered)
or
pyranose
(six-membered),
reflecting the ring size relationship to the common heterocyclic
compounds furan and pyran.
34
During the conversion from straight-chain form to cyclic form, the
carbon atom containing the carbonyl oxygen, called the anomeric
carbon, becomes a chiral center with two possible configurations: the
oxygen atom may take a position either above or below the plane of
the ring. The resulting possible pair of stereoisomers are called
anomers (- anomer and β-anomer).
In the - anomer, the -OH substituent on the anomeric carbon rests on
the opposite side (trans) of the ring from the CH2OH side branch. The
alternative form, in which the CH2OH substituent and the anomeric
hydroxyl are on the same side (cis) of the plane of the ring, is called
the β-anomer.
Because the ring and straight-chain forms readily interconvert, both
anomers exist in equilibrium.
In water solution, glucose can undergo an intramolecular reaction to
yield cyclic hemiacetals. Either five-membered ring hemiacetals (using
35
the hydroxyl group at carbon 4) or six-membered ring hemiacetals
(using the hydroxyl group at carbon 5) can be formed.
36
Ribose, an important aldopentose, commonly adopts a furanose
structure, as shown in the following illustration. By convention for the
D-family, the five-membered furanose ring is drawn in an edgewise
projection with the ring oxygen positioned away from the viewer. The
anomeric carbon atom (colored red here) is placed on the right. The
upper bond to this carbon is defined as beta, the lower bond then is
alpha.
Note that carbon 1 (the aldehyde carbon), which is not chiral in the
open-chain structure, because chiral in the cyclization.
Therefore, a
pair of diastereomers results from the cyclization (called anomers).
A monosaccharide in the form of a five-membered ring hemiacetal is
called a furanose. Similarly, the six-membered ring form is called a
pyranose after pyran.
The terms furanose and pyranose are often
combined with the name of the mono-saccharide- forexample, Dglucopyranose for the six-membered ring of D-glucose, or Dfructofuranose for the five-membered ring of fructose.
The cyclic pyranose forms of various monosaccharides are often drawn
in a flat projection known as a
Haworth formula.
37
The terminal-
CH2OH group is positioned above the plane of the ring in the D-series
and below the plane of the ring in the L-series.
38
Note that any group that is to the right in the Fischer projection is
down in the Haworth projection, and any group that is to the left in the
Fischer projection is up in the Haworth formula.
Mutarotation:
Pure glucose exists in two crystalline forms: -D-glucose and -Dglucose. Pure -D-glucose has a melting point of 146 C. The specific
rotation of a freshly prepared solution is +112. Pure -D-glucose has
a melting point of 150 C. and a specific rotation of +18.7.
The
specific rotation of a solution of either - or -D-glucose changes
39
slowly until it reaches an equilibrium value of +52.6.
This slow
spontaneous change in optical rotation was called mutarotation.
40
Glycosides
When a hemiacetal is treated with an alcohol, an acetal is formed. The
acetals of monosaccharides are called glycosides and have names
ending in -oside.
41
Important reactions of Carbohydrates
Oxidation of monosaccharides:
As noted above, sugars may be classified as reducing or non-reducing
based on their reactivity with Tollens', Benedict's or Fehling's reagents.
If a sugar is oxidized by these reagents it is called reducing, since the
oxidant (Ag+ or Cu+2) is reduced in the reaction, as evidenced by
formation of a silver mirror or precipitation of cuprous oxide. The
Tollens' test is commonly used to detect aldehyde functions; and
because of the facile inter-conversion of ketoses and aldoses under the
basic conditions of this test, ketoses such as fructose also react and are
classified as reducing sugars.
When the aldehyde function of an aldose is oxidized to a
carboxylic acid the product is called an aldonic acid.
If both ends of an aldose chain are oxidized to carboxylic acids
the product is called an aldaric acid. Thus, ribose, xylose, allose and
galactose yield achiral aldaric acids which are, of course, not optically
active. The ribose oxidation is shown in equation 2 below.
1. Aldonic acid
42
2. Aldaric acid
3. Uronic acids:
43
4. Periodic acid oxidation:
The periodic acid oxidation is a test for 1,2-diols and for 1,2- or hydroxy aldehydes and ketones.
A compound containing such a
grouping is oxidized and cleaved by periodic acid.
The
products
of
the
periodic
acid
oxidation
of
glucose
are
formaldehyde and formic acid in the molar ration of 1:5
This oxidation of the CHOH group in glucose to formic acid
can be rationalized by considering the reaction to be
stepwise.
44
5. Effect of concentrated acids on monosaccharides:
Concentrated acids caused dehydration for the monosaccharide leading
to furfural in case of pentoses or 5-hydroxy methyl furfural in case of
hexoses.
45
6. Reduction of monosaccharides:
7. Chain Shortening and Lengthening
These two procedures permit an aldose of a given size to be related to
homologous smaller and larger aldoses.
46
7. Esterification:
8. Acetate formation:
A common reagent for esterification of alcohols is acetic anhydride,
with either sodium acetate or pyridine as an alkaline catalyst.
47
9. Ether formation:
Dimethyl sulfate is an inorganic ester with an excellent leaving group.
This compound is used to form methyl ethers.
Disaccharides
A disaccharides is a carbohydrate composed of two units
of
monosaccharide joined together by a covalent bond known as a
glycoside link from carbon 1 of one unit to an OH of the other unit (via
a dehydration reaction, resulting in the loss of a hydrogen atom from
one monosaccharide and a hydroxyl group from the other). A common
mode of attachment is an  or  glycoside link from the first unit to the
4-hydroxy group of the second unit. This link is called a 1,4-- or a 1,4- link, depending on the stereochemistry at the glycoside carbon.
The formula of unmodified disaccharides is C12H22O11. Although there
are numerous kinds of disaccharides, a handful of disaccharides are
particularly notable.
48
Sucrose:
Sucrose is the most abundant disaccharide and the main form in which
carbohydrates are transported in plants.
The disaccharide sucrose is common table sugar. Whether it comes
from beets or sugar cane, the chemical composition of sucrose is the
same. It is composed of two monosaccharides: D-glucose and
D-
fructose. The glycoside link joins the ketal and acetal carbons;  from
fructose and  from glucose.
The systematic name for sucrose, O-α-D-glucopyranosyl-(1→2)-Dfructofuranoside, indicates four things:
1. Its monosaccharides: glucose and fructose.
2. Their ring types: glucose is a pyranose, and fructose is a furanose.
3. How they are linked together: the oxygen on carbon number 1 (C1)
of
-D-glucose is linked to the C2 of D-fructose.
4. The -oside suffix indicates that the anomeric carbon of both
monosaccharides participates in the glycosidic bond.
Note the difference between sucrose and the other disaccharide is that
both anomeric carbon atoms (not just one) are used in the glycoside
link. In sucrose, neither fructose nor glucose has a hemiacetal group;
49
therefore, sucrose in water is not in equilibrium with an aldehyde or
keto form. Sucrose does not exhibit mutarotation and is not a reducing
sugar.
Invert sugar is a mixture of D-glucose and D-fructose obtained by the
acidic or enzymatic hydrolysis of sucrose. The enzymes that catalyze
the hydrolysis of sucrose, called invertases. Honey is primarily invert
sugar.
Maltose:
The disaccharides maltose is used in baby foods and malted milk. It is
the principal disaccharide obtained from the hydrolysis of starch.
Starch is broken down into maltose in an apparently random fashion by
an enzyme in saliva called -1,4-glucan 4-glucanohydrolase.
A molecule of maltose contains two units of D-glucopyranose. The first
unit is in the form of an -glycoside. This unit is attached to the oxygen
at
carbon 4- in the second unit by a 1,4--  link.
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Cellobiose:
The disaccharide obtained from the partial hydrolysis of cellulose is
called cellobiose.
Like maltose, cellobiose is composed of two
glucopyranose units joined together by a 1,4 - link. Cellobiose differs
from maltose in that the 1,4-linkage is β- rather than -.
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Lactose:
The disaccharide lactose (milk sugar) is different from maltose or
cellobiose in that it is composed of two different monosaccharides, Dglucose and D-galactose.
The systematic name for lactose is O-β-D-galactopyranosyl-(1→4)-Dglucopyranose.
52
Lactose is naturally occurring disaccharide found only in mammal
molecule, occurs naturally in milk. The systematic name for lactose is
O-β-D-galactopyranosyl-(1→4)-D-glucopyranose.s;
human
milk
contain
about
5%
lactose.
cow’s
Lactose
milk
is
and
obtained
commercially as a by-product in the manufacture of cheese.
In normal human metabolism, lactose is hydrolyzed enzymatically to
D-galactose and D-glucose; then the galactose is converted to glucose,
which can undergo metabolism.
A condition called GALACTOSEMIA
that affects some infants is caused by lack of the enzyme used to
concert galactose to glucose. Galactosemia is characterized by high
levels of galactose in the blood and urine.
Symptoms ranges from
vomiting to mental and physical retardation and sometimes death.
Treatment consists of removing milk and milk products from the diet.
(An artificial milk made from soybeans may be substituted.
Polysaccharides:
A polysaccharid is a compound in which the molecules contain many
units of monosaccharid joined together by glycoside links.
Upon
complete hydrolysis, a polysaccharide yields monosaccharides.
Polysaccharides serve three purposes in living systems:
1. Architectural purpose: cellulose gives strength to the plant stems
and branches, chitin serve as structural component of the
exoskeletons of insects.
2. Nutritional purpose: starch is found in wheat and potatoes,
glycogen is an animal’s internal store of readily available
carbohydrate.
3. Specific agents: heparin prevents blood coagulation.
53
Oligosaccharides and polysaccharides are composed of longer chains of
monosaccharide units bound together by glycosidic bonds. The
distinction
between
the
two
is
based
upon
the
number
of
monosaccharide units present in the chain.
Oligosaccharides
typically
contain
between
two
and
nine
monosaccharide units, and polysaccharides contain greater than ten
monosaccharide units. Definitions of how large a carbohydrate must be
to fall into each category vary according to personal opinion.
Starch:
Starch is a polymer of glucose, found in roots, rhizomes, seeds, stems,
tubers
and
corms
of
plants,
as
microscopic
granules
having
characteristic shapes and sizes. Most animals, including humans,
depend on these plant starches for nourishment.
Starch consists of two fractions. About 20% is a water soluble material
called amylose. Molecules of amylose are linear chains of several
thousand glucose units joined by alpha C-1 to C-4 glycoside bonds.
Amylose solutions are actually dispersions of hydrated helical micelles.
The majority of the starch is a much higher molecular weight
substance, consisting of nearly a million glucose units, and called
amylopectin (80%). Molecules of amylopectin are branched networks
built from C-1 to C-4 and
C-1 to C-6 glycoside links, and are
essentially water insoluble.
Amylose is a linear polymer of glucose mainly linked with α-1,4 bonds.
It can be made of several thousands of glucose units. It is one of the
two components of starch, the other being amylopectin.
54
Hydrolysis of starch, usually by enzymatic reactions, produces a syrupy
liquid consisting largely of glucose. When cornstarch is the feedstock,
this product is known as corn syrup. It is widely used to soften texture,
add volume, prohibit crystallization and enhance the flavor of foods.
Glycogen:
Glycogen is the glucose storage polymer used by animals. It has a
structure similar to amylopectin, but is even more highly branched
(about every tenth glucose unit). The degree of branching in these
polysaccharides may be measured by enzymatic or chemical analysis.
55
Cellulose and chitin:
Cellulose and chitin are examples of structural polysaccharides.
Cellulose is used in the cell walls of plants and other organisms, and is
claimed to be the most abundant organic molecule on earth. It has a
variety of uses including in the paper and textile industry and as a
feedstock for the production of rayon (in the viscose process), cellulose
acetate, celluloid and nitrocellulose. Chitin has a similar structure to
cellulose but has nitrogen containing side branches, increasing its
strength. It is found in arthropod exoskeletons and in the cell walls of
some fungi. It has a variety of uses, for example in surgical threads.
56
Over half of the total organic carbon in the earth's biosphere is in
cellulose. Cotton fibres are essentially pure cellulose, and the wood of
bushes and trees is about 50% cellulose.
As a polymer of glucose, cellulose has the formula (C6H10O5)n where n
ranges from 500 to 5,000, depending on the source of the polymer. The
glucose units in cellulose are linked in a linear fashion.
Most animals cannot digest cellulose as a food, and in the diets of
humans this part of our vegetable intake functions as roughage and is
eliminated largely unchanged. Some animals (the cow and termites, for
example) harbor intestinal microorganisms that breakdown cellulose
into monosaccharide nutrients by the use of beta-glycosidase enzymes.
57
Cellulose is commonly accompanied by a lower molecular weight,
branched, amorphous polymer called hemicellulose. In contrast to
cellulose, hemicellulose is structurally weak and is easily hydrolyzed by
dilute acid or base. Also, many enzymes catalyze its hydrolysis.
Hemicelluloses are composed of many D-pentose sugars, with xylose
being the major component. Mannose and mannuronic acid are often
present, as well as galactose and galacturonic acid.
Unlike cellulose, hemicellulose (also a polysaccharide) consists of
shorter chains - 500-3,000 sugar units as opposed to 7,000 - 15,000
glucose molecules per polymer seen in cellulose. In addition,
hemicellulose is a branched polymer, while cellulose is unbranched.
Study problems
1. Draw a Haworth formula of anomers of D-glucopyranose and
D-fructofuranose ?
58
2. There are eight D- aldohexoses and eight L-aldohexoses.
Write Fischer and Haworth progections of D- and L- glucose.
Haworth projection for D- and L-glucose
59
Fischer projection for D- and L- glucose
3. Oxidation of monosaccharides gives different compounds,
e.g. aldonic acid, aldaric acid or uronic acid. Explain ?
60
4. Classify the following monosaccharides (as an aldohexose,
e.g.) and give the number of isomers of each:
61
5. Write equation that illustrate the MUTAROTATION of pure
D-glucose in water ?
62
6. Give the structure of the products for the followings:
D-Glucose +
HIO4
D-Glucose +
[H]
β-D-Glucose +
(CH3 CO)2O
NaO2CCH3
H2O
Starch
H2O
…… …….
…………….
H+ or enzymes
H+ or enzymes
7. Draw 1,4-
Ethanol
enzymes
α-glycoside link in maltose ?
7. What is the difference between each pair of the following?

Lactose and sucrose

Maltose and cellobiose

Amylose and amylopectin
63
2. LIPIDS
Lipids are broadly defined as any fat-soluble naturally-occurring
molecules, such as fats, oils, waxes, cholesterol, sterols, vitamins A, D,
E and K, glycerols, phospholipids, and others.
64
Biological functions of lipids:
1. Acting as structural components of cell membranes.
Phospholipids are lipids that contain phosphate ester groups.
The
phospholipids are the main structural component of biological
membranes,
such
as
the
cellular
plasma
membrane
and
the
intracellular membranes of organelles. In animal cells the plasma
membrane physically separates the intracellular components from the
extracellular environment.
Phospholipids are made from glycerol, two fatty acids, and (in place of
the third fatty acid) a phosphate group with some other molecule
attached to its other end (e.g. acetyl choline or ethanol amine). The
hydrocarbon tails of the fatty acids are hydrophobic, but the phosphate
group
end
of
the
molecule
is
hydrophilic.
This
means
that
phospholipids are soluble in both water and oil.
A biological membrane is a form of lipid bilayers. In an aqueous
system, the polar heads of lipids orientate towards the polar, aqueous
environment, while the hydrophobic tails minimize their contact with
water. Cell membranes are made mostly of phospholipids arranged in
65
a double layer with the tails from both layers “inside” (facing toward
each
other)
and
the
heads
facing
environment) on both surfaces.
66
“out”
(toward
the
watery
2. Energy storage and metabolism.
Triacylglycerols, stored in adipose tissue, are a major form of energy
storage in animals. Animals use triglycerides for energy storage
because of its high caloric content (9 KCal/g).
Triglycerides and phospholipids are broken down into free fatty acids
by the action of lipases. Beta oxidation is the process by which fatty
acids, in the form of acyl-CoA molecules, are broken down in the
mitochondria and/or in peroxisomes to generate acetyl-CoA.
The acetyl CoA is then ultimately converted into ATP, CO2 , and H2O
using the citric acid cycle and the electron transport chain.
Conversely, fatty acid biosynthesis takes place in the cytoplasm, using
acetyl-CoA (derived from carbohydrates, amino acids or fatty acids) as
the precursor. The fatty acids may be subsequently converted to
triacylglycerols that are packaged in lipoproteins and secreted from the
liver.
Many lipids are absolutely essential for life. However,
there is also considerable awareness:

Abnormal levels of certain lipids, particularly cholesterol (in
hypercholesterolemia) and trans fatty acids, are risk factors for
heart disease amongst others.

Humans have a requirement for certain essential fatty acids, such
as linoleic acid (omega-6 fatty acid) and α-linolenic acid
(omega-3 fatty acid) in the diet because they cannot be
synthesized from simple precursors in the diet.

Both of these fatty acids are 18-carbon polyunsaturated fatty
acids differing in the number and position of the double bonds.
Most vegetable oils are rich in linoleic acid (sunflower, and corn
oils). α-linolenic acid is found in the green leaves of plants, and in
67
selected seeds, nuts and legumes (flax, canola, walnuts and soy).
Fish oils are particularly rich in the longer-chain omega-6 fatty
acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA).

Most of the lipid found in food is in the form of triacylglycerols,
cholesterol and phospholipids.

Most of the saturated fatty acids (as triacylglycerols) in the diet
are incorporated into adipose tissue stores, because the absence
of double bonds allows a higher energy yield per carbon than is
obtained from oxidation of unsaturated fatty acids.

The
longer
chain
fatty
acids
are
incorporated
into
cell
membranes as phospholipids regardless of degree of saturation.

Dietary fat provides an average energy intake which is
approximately twice that of carbohydrate or protein.

A minimum amount of dietary fat is necessary to facilitate
absorption of fat-soluble vitamins (A, D, E and K) and
carotenoids.

A minimal amount of body fat is also necessary to provide
insulation that prevents heat loss and protects vital organs from
shock due to ordinary activities.

High fat intake contributes to increased risk of obesity, diabetes
and atherosclerosis. Atherosclerosis is the primary cause of
coronary and cardiovascular diseases and is primarly due to the
buildup of plaque on the inside walls of arteries.

Plaque is made up of cholesterol-rich low density lipoproteins
(LDL).

Saturated fats have a profound hypercholesterolemic (increase
blood cholesterol levels) effect and tend to increase plasma LDL.
They are found predominantly in animal products (butter, cheese
and meat).
68

Intake of monounsaturated fats in oils such as olive oil is thought
to be preferable to consumption of polyunsaturated fats in oils
such as corn oil because the monounsaturated fats apparently do
not lower high-density-lipoprotein (HDL) cholesterol levels.
Keeping cholesterol in the normal range not only helps prevent
heart attacks and strokes but may also prevent the progression
of atherosclerosis.
Lipids are consists of the following:
1. Fats and oils
2. waxe
3. phospholipids
4. steroids (like cholesterol)
5. some other related compounds.
Fats and Oils
Fats and oils are made from two kinds of molecules: glycerol (a type of
alcohol with a hydroxyl group on each of its three carbons) and three
fatty acids joined by dehydration synthesis. Since there are three fatty
acids attached, these are known as triglycerides.
Triglycerides or triacylglycerol
69
The distinction between a fat and oil is arbitrary (random): at room
temperature a fat is solid and an oil is liquid.
Most glycerides in
animals are fats, while those in plants tend to be oil; hence the terms
animal fats (beef fat) and vegetable oils (corn oil, sunflower oil).
The carboxylic acid obtained from the hydrolysis of a fat or oil, called a
fatty acid, generally has a long, unbranched hydrocarbon chain. Fats
and oils are often named as derivatives of these fatty acids.
Most naturally occurring fats and oils are mixed triglycerides- that is,
the three fatty-acid portions of the glyceride are not the same.
Almost all naturally occurring fatty acids have an even number of
carbon atoms because they are biosynthesized from the two-carbon
acetyl groups in acetylcoenzyme A.
70
The rate of fatty acid synthesis is controlled by the equilibrium
between monomeric acetyl Co-A carboxylase (ACC) and polymeric ACC.
The activity of ACC requires polymerization. This conformational
change is enhanced by citrate and inhibited by long-chain fatty acids.
The synthesis of fatty acids from acetyl-CoA and malonyl-CoA is carried
out by fatty acid synthase (FAS).
The primary fatty acid synthesized by fatty acid synthase (FAS) is
palmitate
enzyme
CH3 (CH2)14 COO- .
and
can
then
Palmitate is then released from the
undergo
separate
unsaturation to yield other fatty acid molecules.
Structure of Fatty Acids
71
elongation
and/or
The “tail” of a fatty acid is a long hydrocarbon chain, making it
hydrophobic. The “head” of the molecule is a carboxyl group which is
hydrophilic.
Fatty acids are the main component of soap, where their tails are
soluble in oily dirt and their heads are soluble in water to emulsify and
wash away the oily dirt. However, when the head end is attached to
glycerol to form a fat, that whole molecule is hydrophobic.
The terms saturated, mono-unsaturated, and poly-unsaturated refer to
the number of hydrogens attached to the hydrocarbon tails of the fatty
acids as compared to the number of double bonds between carbon
atoms in the tail.
Fats, which are mostly from animal sources, have all single bonds
between the carbons in their fatty acid tails, thus all the carbons are
also bonded to the maximum number of hydrogen possible. Since the
fatty acids in these triglycerides contain the maximum possible amount
of hydrogen, these would be called saturated fats.
The hydrocarbon chains in these fatty acids are, thus, fairly straight
and can pack closely together, making these fats solid at room
temperature.
72
Oils, mostly from plant sources, have some double bonds between
some of the carbons in the hydrocarbon tail, causing bends or “kinks”
in the shape of the molecules. Because some of the carbons share
double bonds, they’re not bonded to as many hydrogen’s as they could
if they weren’t double bonded to each other. Therefore these oils are
called unsaturated fats. Because of the kinks in the hydrocarbon tails,
unsaturated fats can’t pack as closely together, making them liquid at
room temperature.
Many people have heard that the unsaturated fats are “healthier” than
the saturated ones. Hydrogenated vegetable oil (as in shortening and
commercial peanut butters where a solid consistency is needed)
started out as “good” unsaturated oil. However, this commercial
product has had all the double bonds artificially broken and hydrogen’s
artificially added to turn it into saturated fat that bears no resemblance
to the original oil from which it came (so it will be solid at room
temperature).
In unsaturated fatty acids, there are two ways the pieces of the
hydrocarbon tail can be arranged around a C=C double bond. In cis
bonds, the two pieces of the carbon chain on either side of the double
bond are either both “up” or both “down,” such that both are on the
same side of the molecule.
73
In trans bonds, the two pieces of the molecule are on opposite sides of
the double bond, that is, one “up” and one “down” across from each
other.
Naturally-occurring unsaturated vegetable oils have almost all cis
bonds, but using oil for frying causes some of the cis bonds to convert
to trans bonds. If oil is used only once like when you fry an egg, only a
few of the bonds do this so it’s not too bad. However, if oil is constantly
re-used, like in fast food French fry machines, more and more of the cis
bonds are changed to trans until significant numbers of fatty acids with
trans bonds build up.
The reason this is of concern is that fatty acids with trans bonds are
carcinogenic, or cancer-causing. The levels of trans fatty acids in
highly-processed, lipid-containing products such as margarine are
quite high.
We need fats in our bodies and in our diet. Animals in general use fat
for energy storage because fat stores 9 KCal/g of energy. Plants, which
don’t move around, can afford to store food for energy in a less
compact but more easily accessible form, so they use starch for energy
storage.
74
Carbohydrates and proteins store only 4 KCal/g of energy, so fat stores
over twice as much energy/gram as fat. By the way, this is also related
to the idea behind some of the high-carbohydrate weight loss diets.
The human body burns carbohydrates and fats for fuel in a given
proportion to each other. The theory behind these diets is that if they
supply carbohydrates but not fats, then it is hoped that the fat needed
to balance with the sugar will be taken from the dieter’s body stores.
Fat is also is used in our bodies to:

Cushion (soften) vital organs like the kidneys.

Serve as insulation, especially just beneath the skin.
Examples Of Fatty Acids:
75
The higher melting points of the saturated fatty acids (solid) reflect the
uniform rod-like shape of their molecules. The cis-double bond(s) in
the unsaturated fatty acids introduce a kink (bend) in their shape,
which makes it more difficut to pack their molecules together in a
stable repeating array or crystalline lattice.
The trans-double bond isomer of oleic acid, known as elaidic acid, has a
linear shape and a melting point of 45 ºC (32 ºC higher than its cis
isomer). The shapes of stearic and oleic acids are shown below.
76
The configuration around any double bond in a naturally occurring
fatty acid is cis, a configuration that results in the low melting points of
oils. A saturated fatty acid forms zigzag chains that can fit compactly
together, resulting in high Van der Waals attractions; therefore,
saturated fats are solids. If a few cis double bonds are present in the
chains, the molecules cannot form neat, compact lattices, but tend to
be oil. ; polyunsaturated triglycerides tend to be oils.
Soaps and Detergents
Soaps are the alkali metal salts (usually sodium salts) of fatty acids.
Carboxylic acids and salts having alkyl chains longer than eight
carbons exhibit unusual behavior in water due to the presence of both
hydrophilic (CO2) and hydrophobic (alkyl) regions in the same
molecule. Such molecules are termed amphiphilic (Gk. amphi = both)
or amphipathic. Fatty acids made up of ten or more carbon atoms are
nearly insoluble in water, and because of their lower density, float on
the surface when mixed with water. Unlike paraffin or other alkanes,
which tend to (pond or spot)) puddle on the waters surface, these fatty
acids spread evenly over an extended water surface, eventially forming
a monomolecular layer in which the polar carboxyl groups are
hydrogen bonded at the water interface, and the hydrocarbon chains
77
are aligned together away from the water. Substances that accumulate
at water surfaces and change the surface properties are called
surfactants.
78
Alkali metal salts of fatty acids are more soluble in water than the acids
themselves, and the amphiphilic character of these substances also
make them strong surfactants. The most common examples of such
compounds are soaps and detergents, four of which are shown below.
Note that each of these molecules has a nonpolar hydrocarbon chain,
the "tail", and a polar (often ionic) "head group". The use of such
compounds as cleaning agents is facilitated by their surfactant
character, which lowers the surface tension of water, allowing it to
penetrate and wet a variety of materials.
Very small amounts of these surfactants dissolve in water to give a
random
dispersion
of
solute
molecules.
79
However,
when
the
concentration is increased an interesting change occurs. The surfactant
molecules reversibly assemble into poly-molecular aggregates called
micelles. By gathering the hydrophobic chains together in the center of
the micelle, disruption of the hydrogen bonded structure of liquid
water is minimized, and the polar head groups extend into the
surrounding water where they participate in hydrogen bonding.
These micelles are often spherical in shape, but may also assume
cylindrical and branched forms. Here the polar head group is
designated by a blue circle, and the nonpolar tail is a zig-zag black line.
An animated display of micelle formation is presented below. Micelles
are able to encapsulate non-polar substances such as grease within
their hydrophobic center, and thus solubilize it so it is removed with
the wash water. Since the micelles of anionic amphiphiles have a
negatively charged surface, they repel one another and the non-polar
dirt is effectively emulsified. To summarize, the presence of a soap or a
detergent in water facilitates the wetting of all parts of the object to be
cleaned, and removes water-insoluble dirt by incorporation in micelles.
80
The oldest amphiphilic cleaning agent known to humans is soap.
Soap is manufactured by the base-catalyzed hydrolysis (saponification)
of animal fat.
Fat is heated with lye (sodium hydroxide) and is thus saponified to
glycerol and sodium salts of fatty acids.
Before sodium hydroxide was commercially available, a boiling solution
of potassium carbonate leached from wood ashes was used. Soft
potassium soaps were then converted to the harder sodium soaps by
washing with salt solution.
The importance of soap to human civilization is documented by history,
but some problems associated with its use have been recognized. One
of these is caused by the weak acidity (pKa ca. 4.9) of the fatty acids.
Solutions of alkali metal soaps are slightly alkaline (pH 8 to 9) due to
hydrolysis. If the pH of a soap solution is lowered by acidic
contaminants, insoluble fatty acids precipitate and form a scum. A
second problem is caused by the presence of calcium and magnesium
81
salts in the water supply (hard water). These divalent cations cause
aggregation of the micelles, which then deposit as a dirty scum.
These problems have been alleviated by the development of synthetic
amphiphiles called detergents (or syndets). By using a much stronger
acid for the polar head group, water solutions of the amphiphile are
less sensitive to pH changes. Also the sulfonate functions used for
virtually all anionic detergents confer greater solubility on micelles
incorporating the alkaline earth cations found in hard water. Variations
on the amphiphile theme have led to the development of other classes,
such as the cationic and nonionic detergents shown above.
Cationic detergents often exhibit germicidal properties, and their
ability to change surface pH has made them useful as fabric softners
and
hair
conditioners.
These
versatile
chemical
"tools"
have
dramatically transformed the household and personal care cleaning
product markets over the past fifty years.
82
Phospholipids
Phospholipids are lipids that contain phosphate ester groups. They are
the main constituents of cell membranes.
83
Phospholipids are made from glycerol, two fatty acids, and (in place of
the third fatty acid) a phosphate group with some other molecule
attached to its other end. The hydrocarbon tails of the fatty acids are
still hydrophobic, but the phosphate group end of the molecule is
hydrophilic because of the oxygen’s with all of their pairs of unshared
electrons. This means that phospholipids are soluble in both water and
oil.
Phosphoglycerides , one type of phospholipids, are closely related to
the fats and oils. These compounds usually contain fatty-acid esters at
two positions of glycerol with a phosphate ester at the third position.
Phosphoglycerides are distinctive (unique) because their molecules
contain two long hydrophobic tails and a highly polar hydrophilic group
– a diploar-ion group.
Phosphoglycerides are, therefore, neutral
surfactants. They are excellent emulsifying agents. In mayonnaise, the
84
phosphoglycerides of the egg yolk keep the vegetable oil emulsified in
the vinegar.
There are two types of phosphoglyceride (lecithins and cephalins) that
are found principally in the brain, nerve cells, and liver of animals and
are also found in egg yolks, wheat germ, yeast, soybeans, and other
foods.
These two types of compounds are similar to each other in
structure.
1. LECITHINS (Phosphatidylcholine) are derivatives of choline chloride,
HOCH2CH2N(CH3)3
+
Cl- , which is involved in the transmission of nerve
impulses.
2.
CEPHALINS
(Phosphatidylethanolamine)
are
derivatives
of
ethanolamine, HOCH2CH2NH2.
Other classes of phospholipids are represented by plasmalogens, which
have vinyl ether group instead of ester groups at carbon 1 of glycerol,
and sphingolipids, of which sphingomyelin is an example.
85
Phospholipids aggregate or self-assemble when mixed with water, but
in a different manner than the soaps and detergents. Because of the
two pendant alkyl chains present in phospholipids and the unusual
mixed charges in their head groups, micelle formation is unfavorable
relative to a bilayer structure.
If a phospholipid is smeared over a small hole in a thin piece of plastic
immersed in water, a stable planar bilayer of phospholipid molecules is
created at the hole. As shown in the following diagram, the polar head
groups on the faces of the bilayer contact water, and the hydrophobic
alkyl chains form a nonpolar interior. The phospholipid molecules can
move about in their half the bilayer, but there is a significant energy
barrier preventing migration to the other side of the bilayer.
86
This bilayer membrane structure is also found in aggregate structures
called liposomes. Liposomes are microscopic vesicles consisting of an
aqueous core enclosed in one or more phospholipid layers. They are
formed when phospholipids are vigorously mixed with water. Unlike
micelles, liposomes have both aqueous interiors and exteriors.
Terpenes
Compounds classified as terpenes constitute what is arguably the
largest and most diverse class of natural products. A majority of these
compounds are found only in plants, but some of the larger and more
complex terpenes ( e.g. squalene & lanosterol ) occur in animals.
Terpenes incorporating most of the common functional groups are
known, so this does not provide a useful means of classification.
Instead, the number and structural organization of carbons is a
definitive characteristic.
Terpenes may be considered to be made up of isoprene ( more
accurately isopentane ) units, an empirical feature known as the
87
isoprene rule. Because of this, terpenes usually have 5n carbon atoms
( n is an integer ).
Terpenes are subdivided as follows:
Isoprene itself, a C5H8 gaseous hydrocarbon, is emitted by the leaves of
various plants as a natural byproduct of plant metabolism. Next to
methane it is the most common volatile organic compound found in the
armosphere. Examples of C10 and higher terpenes, representing the
four most common classes are shown in the following diagram. The
initial display is of monoterpenes; larger terpenes will be shown. Most
terpenes may be structurally dissected into isopentane segments.
88
The isopentane units in most of these terpenes are easy to discern, and
are defined by the shaded areas. In the case of the monoterpene
camphor, the units overlap to such a degree it is easier to distinguish
them by coloring the carbon chains. This is also done for alpha-pinene.
In the case of the triterpene lanosterol we see an interesting deviation
from the isoprene rule. This thirty carbon compound is clearly a
terpene, and four of the six isopentane units can be identified.
However, the ten carbons in center of the molecule cannot be disected
in this manner.
Polymeric isoprenoid hydrocarbons have also been identified. Rubber is
undoubtedly the best known and most widely used compound of this
kind. It occurs as a colloidal suspension called latex in a number of
plants, ranging from the dandelion to the rubber tree (Hevea
brasiliensis). Rubber is a polyene, and exhibits all the expected
reactions of the C=C function. Bromine, hydrogen chloride and
hydrogen all add with a stoichiometry of one molar equivalent per
89
isoprene unit. Ozonolysis of rubber generates a mixture of levulinic
acid ( CH3COCH2CH2CO2H ) and the corresponding aldehyde. Pyrolysis of
rubber produces the diene isoprene along with other products.
The double bonds in rubber all have a Z-configuration, which causes
this macromolecule to adopt a kinked or coiled conformation. This is
reflected in the physical properties of rubber. Despite its high
molecular weight (about one million), crude latex rubber is a soft,
sticky, elastic substance. Chemical modification of this material is
normal for commercial applications. Gutta-percha (structure above) is
a naturally occuring E-isomer of rubber. Here the hydrocarbon chains
adopt a uniform zig-zag or rod like conformation, which produces a
more rigid and tough substance. Uses of gutta-percha include electrical
insulation and the covering of golf balls.
90
Pheromones
Humans communicate by talking, using sign language, painting
pictures, or writing letters (or books). But insects and some animals
also communicate, in part, by chemicals.
91
A chemical secreted by one individual of a species the brings forth a
response in another individual of the same species is called a
pheromone.
Insect pheromones called alarm pheromones signify
danger. For example, a pheromone secreted by one bee helps alert
other bees to the location of a food source. Insect sex attractants are
another class of pheromones.
Sex-attractant pheromones have been used for insect control. In some
cases, male insects may be lured by a sex-attractant pheromone,
trapped, and then sterilized and released to mate unproductively with
the females.
Many insect pheromones are not complex in structure. Geranitol and
citral, both terpenes, are recruiting pheromones for honeybees, while
isoamyl acetate (not a terpene) is a bee alarm pheromone.
Steroids
The important class of lipids called steroids are actually metabolic
derivatives of terpenes, but they are customarily treated as a separate
group.
92
Steroids may be recognized by their tetracyclic skeleton, consisting of
three fused six-membered and one five-membered ring.
The four rings are designated A, B, C & D as noted, and the peculiar
numbering of the ring carbon atoms (shown in red) is the result of an
earlier misassignment of the structure. The substituents designated by
R are often alkyl groups, but may also have functionality. The R group
at the A:B ring fusion is most commonly methyl or hydrogen, that at
the C:D fusion is usually methyl. The substituent at C-17 varies
considerably, and is usually larger than methyl if it is not a functional
group. The most common locations of functional groups are C-3, C-4,
C-7, C-11, C-12 & C-17. Ring A is sometimes aromatic. Since a number
of tetracyclic triterpenes also have this tetracyclic structure, it cannot
be considered a unique identifier.
Some important steroids
1. Cholesterol
It is the most widespread animal steroid and is found in almost all
animal tissues.
Human gallstones and egg yolks are especially rich
sources of this compound.
Cholesterol is a necessary intermediate in the biosynthesis of the
steroid hormones; however, since it can be synthesized from
acetylcoenzyme A, it is not a dietary necessity. High levels of blood
cholesterol are associated with arteriosclerosis (hardening of the
arteries), a condition in which cholesterol and other lipids coat the
insides of the arteries.
2. Cortisone and cortisol
These hydrocortisone are two of 28 or more hormones secreted by the
adrenal cortex. Both these steroids alter protein, carboxylate, and lipid
93
metabolism in ways not entirely understood. They are widely used to
treat inflammation due to allergies or rheumatoid arthritis.
3. Sex hormones
They are produced primarily in the testes or the ovaries; their
production is regulated by pituitary hormones.
The sex hormones
impart secondary sex characteristics and regulate the sexual and
reproductive
functions.
Male
hormones
are
collectively
called
androgens; female hormones, estrogens; and pregnancy hormones,
progestins.
94
4. Bile acids
They are found in bile, which is produced in the liver and stored in the
gall bladder. The structure of cholic acid, the most abundant bile acid,
follows.Bile acids are secreted into the intestines in combination with
sodium salts of either glycine or taurine.
The bile acid-amino acid link is an amide link between the carboxyl
group of the bile and the amino group of the amino acid. In this
combined form, the bile acid-amino acid acts to keep lipids emulsified
in the intestines, thereby promoting their digestion.
95
Lipid Soluble Vitamins
The essential dietary substances called vitamins are commonly
classified as "water soluble" or "fat soluble". Water soluble vitamins,
such as vitamin C, are rapidly eliminated from the body and their
dietary levels need to be relatively high. The lipid soluble vitamins are
not as easily eliminated and may accumulate to toxic levels if
consumed in large quantity. They are vitamin A, vitamin D, vitamin E
and vitamin K.
From this data it is clear that vitamins A and D, while essential to good
health in proper amounts, can be very toxic. Vitamin D, for example, is
used as a rat poison, and in equal weight is more than 100 times as
poisonous as sodium cyanide.
96
From the structures shown here, it should be clear that these
compounds have more than a solubility connection with lipids.
Vitamins A is a terpene, and vitamins E and K have long terpene chains
attached to an aromatic moiety. The structure of vitamin D can be
described as a steroid in which ring B is cut open and the remaining
three rings remain unchanged. The precursors of vitamins A and D
have been identified as the tetraterpene beta-carotene and the steroid
ergosterol, respectively.
Waxes
Waxes are esters of fatty acids with long chain monohydric alcohols
(one hydroxyl group). Natural waxes are often mixtures of such esters,
and may also contain hydrocarbons. The formulas for three well known
waxes are given below, with the carboxylic acid moiety and the alcohol
moiety.
97
Waxes are widely distributed in nature. The leaves and fruits of many
plants have waxy coatings, which may protect them from dehydration
and small predators. The feathers of birds and the fur of some animals
have similar coatings which serve as a water repellent. Carnuba wax is
valued for its toughness and water resistance.
98
Study problems:
1. Compare between each pair of the followings:
Fat
Oil
Pheromones
Sex hormones
Sesquiterpenes
Monoterpenes
2. Draw the structure of the followings:
The ring system of all steroids
Dipeptide
Isoprene unit
Neutral amino acid
One of the terpenes
One of the pheromones
99
Phosphoglyceride
Uronic acid
3-Match each of the following on the right:
1
Cholesterol
Is a steroid hormone
2
Testosterone
Phosphoglycerides
3
Pheromones
Lipid
4
Corn oil
The monomer of terpenes
5
Lecithin
Fatty acid
6
Isoprene
Synthesized from acetyl Co-A
7
Oleic acid
Geranitol
100
3. PROTEINS
Proteins are large organic compounds made of amino acids arranged in
a linear chain and joined together by peptide bonds between the
carboxyl and amino groups of adjacent amino acid residues. Proteins
are polyamides, and hydrolysis of a protein yields amino acids.
101
Like other biological macromolecules such as polysaccharides and
nucleic acids, proteins are essential parts of organisms and participate
in every process within cells. Many proteins are enzymes that catalyze
biochemical reactions and are vital to metabolism.
Proteins also have structural or mechanical functions, such as actin and
myosin in muscle and the proteins in the cytoskeleton, which form a
system of scaffolding that maintains cell shape. Other proteins are
important in cell signaling, immune responses, cell adhesion, and the
cell cycle.
Proteins are also necessary in animals' diets, since animals cannot
synthesize all the amino acids they need and must obtain essential
amino acids from food. Through the process of digestion, animals break
102
down ingested protein into free amino acids that are then used in
metabolism.
Proteins are linear polymers built from 20 different
-amino acids.
These amino acids are commonly found in plant and animal proteins,
yet these 20 amino acids can be combined in a variety of ways to form
muscles,
tendons,
skin,
fingernails,
feathers,
silk,
hemoglobin,
enzymes, antibodies, and many hormones.
The structure of amino acids:
The amino acids found in proteins are -amino carboxylic acids. All
amino acids possess common structural features, including an
-carbon to which an amino group, a carboxyl group, and a variable
side chain are bonded. Only proline differs from this basic structure as
it contains an unusual ring to the N-end amine group, which forces the
CO–NH amide moiety into a fixed conformation.
The side chains of the standard amino acids, detailed in the list of
standard amino acids, have different chemical properties that produce
three-dimensional protein structure and are therefore critical to
protein function.
The amino acids in a polypeptide chain are linked by peptide bonds
formed in a dehydration reaction. Once linked in the protein chain, an
individual amino acid is called a residue,
and the linked series of
carbon, nitrogen, and oxygen atoms are known as the main chain or
protein backbone.
103
Due to the chemical structure of the individual amino acids, the protein
chain has directionality. The end of the protein with a free carboxyl
group is known as the C-terminus or carboxy terminus, whereas
the end with a free amino group is known as the N-terminus or
amino terminus.
The commonly occurring amino acids are of 20 different kinds which
contain the same dipolar ion group
H3N+.CH.COO-. They all have in
common a central carbon atom to which are attached a hydrogen
atom, an amino group (NH2) and a carboxyl group (COOH). The central
carbon atom is called the Calpha-atom and is a chiral centre. All amino
acids found in proteins encoded by the genome have the Lconfiguration at this chiral centre.
Amino acids in proteins (or polypeptides) are joined together by
peptide bonds. The sequence of R-groups along the chain is called the
primary structure.
104
The simplest amino acid is amino acetic acid
(H2NCH2CO2H), called
glycine, which has no side chain and consequently does not contain a
chiral carbon. All other amino acids have side chains, and therefore
their -carbons are chiral.
Isomerism
Of the standard -amino acids, all but glycine can exist in either of two
optical isomers, called L- or D-amino acids, which are mirror images of
each other. While L-amino acids represent all of the amino acids found
in proteins during translation in the ribosome, D-amino acids are found
in some proteins produced by enzyme post-translational modifications
after translation and translocation to the endoplasmic reticulum, as in
exotic sea-dwelling organisms such as cone snails. They are also
abundant components of the peptidoglycan cell walls of bacteria, and
D-serine may act as a neurotransmitter in the brain.
The L and D convention for amino acid configuration refers not to the
optical activity of the amino acid itself, but rather to the optical activity
of the isomer of glyceraldehyde from which that amino acid can
105
theoretically
be
synthesized
(D-glyceraldehyde
L-glyceraldehyde is levorotary).
The two optical isomers
106
is
dextrorotary;
Amino acids from proteins belong the L-series- that is, the groups
around the -carbon have the same configuration as L-glyceraldehyde.
Amino acids do not always behave like organic compounds because:
1. They have melting points of over 200 , whereas most organic
compounds of similar molecular weight are liquids at room
temperature.
2. Amino acids are soluble in water and other polar solvents, but
insoluble in non-polar solvents such as diethyl ether or benzene.
3. Amino acids have large dipole moments.
4. They are less acidic than most carboxylic acids and less basic
than most amines.
Why do amino acids exhibit such unusual properties?
The reason is
that an amino acid contains a basic amino group and an acidic carboxyl
group in the same molecule. An amino acid undergoes an internal acidbase reaction to yield a dipolar ion, also called a zwitter ion.
107
Because of the resultant ionic charges, an amino acid has many
properties of a salt. Furthermore, the pKa of an amino acid is not the
pKa of a –COOH group, but that of an -NH3
+
group. The pKb is not
that of a basic amino group, but that of the very weakly basic –COOgroup.
108
ISOELECTRIC POINT
Amino acids have both amine and carboxylic acid functional groups and
are therefore both an acid and a base at the same time. At a certain pH
known as the isoelectric point an amino acid has no overall charge,
since the number of protonated ammonia groups (positive charges)
and deprotonated carboxylate groups (negative charges) are equal.
109
The amino acids all have different isoelectric points. The ions produced
at the isoelectric point have both positive and negative charges and are
known as a zwitter ion, which comes from the German word Zwitter
meaning "hermaphrodite" or "hybrid". Amino acids can exist as zwitter
ions in solids and in polar solutions such as water, but not in the gas
phase. Zwitter ions have minimal solubility at their isolectric point and
an amino acid can be isolated by precipitating it from water by
adjusting the pH.
Essential and non-essential amino acids
Amino acids are join together to form short polymer chains called
peptides or longer chains called either polypeptides or proteins.
These polymers are linear and un-branched, with each amino acid
within the chain attached to two neighboring amino acids.
When taken up into the human body from the diet, amino acids are
either used to synthesize proteins and other biomolecules or oxidized
to urea and carbon dioxide as a source of energy. The oxidation
pathway
starts
with
the
removal
of
the
amino
group
by
a
transaminase, the amino group is then fed into the urea cycle. The
other product of transamidation is -keto acid that enters the citric
acid cycle.
Of the twenty amino acids, eight are called essential amino acids
because the human body cannot synthesize them from other
compounds at the level needed for normal growth, so they must be
obtained from food. However, the rest can be synthesized in our body
and therefore named non-essential amino acids.
110
Individual differences in requirements for amino acids:
The amino acid tyrosine is conditionally non-essential where in most
people, tyrosine can be synthesized from phenylalanine.
A small
percent of individuals who have inherited a condition known as
phenylketonuria (PKU), which means “phenyl ketones in the urine,” do
not have the enzyme phenylalanine hydroxylase necessary for this
conversion.
In these people, the phenylalanine is converted to
phenylpyruvic acid.
The diet of a person with PKU must contain some tyrosine and must
also be limited in its quantity of phenylalanine; otherwise, excessive
amounts of phenylpyruvic acid accumulate in the brain, causing mental
retardation.
111
The structure of the common amino acids found in proteins are:
112
Importance of side chain:
There are three types of amino acids:
1. Acidic amino acids: They contain more carboxyl groups in their
side chain.
2. Basic amino acids: They contain more amino groups in their side
chain.
113
3. Neutral amino group: They contain groups other than acidic or
amino in their side chains. They divided into two categories:
a)-Polar neutral amino acids: They contain –OH, -SH, or other
polar groups
b)-Non-polar neutral amino acids: They contain non-polar
groups.
114
This side chains of amino acids determine the structure reactivity and
the characteristic of the protein.
The order in which amino acids are found in a protein molecule
determines the relationship of the side chains to one another and
consequently determines how the protein interacts with itself and with
its environment.
For example , a hormone or other water-soluble protein contains many
amino acids with polar side chains, while an insoluble muscle protein
contains a greater proportion of amino acids with nonpolar side chains.
Synthesis of amino acids:
1) Amination of alpha-bromocarboxylic acids:
The bromoacids, in turn, are conveniently prepared from carboxylic acids by reaction
with Br2 + PCl3. Although this direct approach gave mediocre results when used
to prepare simple amines from alkyl halides, it is more effective for making amino
acids, thanks to the reduced nucleophilicity of the nitrogen atom in the product.
Nevertheless, more complex procedures that give good yields of pure compounds
are often chosen for amino acid synthesis.
2) By modifying the nitrogen as a phthalimide salt:
This procedure, known as the Gabriel synthesis, can be used to advantage in
aminating bromo malonic esters. Since the phthalimide substituted malonic ester has
an acidic hydrogen, activated by the two ester groups, this intermediate may be
converted to an ambident anion and alkylated. Finally, base catalyzed hydrolysis of
the phthalimide moiety and the esters, followed by acidification and thermal
decarboxylation, produces an amino acid and phthalic acid (not shown).
115
3.An elegant procedure, known as the Strecker
synthesis:
Assembles an alpha-amino acid from ammonia, cyanide and an aldehyde. This
reaction (shown below) is essentially an imino analog of cyanohydrin formation. The
alpha-amino nitrile formed in this way can then be hydrolyzed to an amino acid by
either acid or base catalysis.
3.
Resolution
The racemic amino acid is first converted to a benzamide derivative to remove the
basic character of the amino group. Next, an ammonium salt is formed by combining
the carboxylic acid with an optically pure amine, such as brucine (a relative of
strychnine).
116
Reaction of amino acids:
1. Amphoterism of amino acids:
As amino acids have both a primary amine group and a primary
carboxyl group, therefore, an amino acid is amphoteric: it can undergo
reaction with either an acid or a base to yield a cation or an anion,
respectively.
2. Acylation of amino acids:
The amino group of an amino acid can be readily acylated with either
an acid halide or an acid anhydride to yield an amide.
117
3. Reaction with ninhydrin:
Amino acids react with ninhydrin to form a blue-violet product called
Ruhemann’s purple. The reaction is commonly used as a spot test to
detect the presence of amino acids on chromatography paper.
118
4.Carboxylic acid esterification:
5.Oxidative coupling:
Peptide bond formation
The condensation of two amino acids to form a peptide bond are
carried as described below:
119
As both the amine and carboxylic acid groups of amino acids can react
to form amide bonds, one amino acid molecule can react with another
and become joined through an amide linkage. This polymerization of
amino acids is what creates proteins. This condensation reaction yields
the newly formed peptide bond and a molecule of water.
Chemical synthesis of proteins
Short proteins can also be synthesized chemically by a family of
methods known as peptide synthesis, which rely on organic synthesis
techniques such as chemical legation to produce peptides in high yield.
Chemical synthesis allows for the introduction of non-natural amino
acids into polypeptide chains, such as attachment of fluorescent probes
to amino acid side chains. These methods are useful in laboratory
biochemistry and cell biology, though generally not for commercial
applications. Chemical synthesis is inefficient for polypeptides longer
than about 300 amino acids, and the synthesized proteins may not
readily assume their native tertiary structure. Most chemical synthesis
methods proceed from C-terminus to N-terminus, opposite the
biological reaction.
Structure of proteins
Most proteins fold into unique 3-dimensional structures. The shape into
which a protein naturally folds is known as its native state.
Biochemists often refer to four distinct aspects of a protein's structure
(Higher structure of proteins):
1. Primary structure:
The sequence of amino acids in a protein
molecule is called the primary structure of the protein.
120
The primary structure of a segment of a polypeptide chain or of a
protein is the amino-acid sequence of the polypeptide chain(s), without
regard to spatial arrangement (apart from configuration at the alphacarbon atom).
2. Secondary structure:
regularly repeating local structures
stabilized by hydrogen bonds. The most common examples are the
alpha helix and beta sheet. Because secondary structures are local,
many regions of different secondary structure can be present in the
same protein molecule.
The common secondary structures in proteins are namely -helix,
-sheets and turns.
Anti-parallel beta-sheets are more often twisted than parallel sheets.
Turns are the third of the three "classical" secondary structures that
serve to reverse the direction of the polypeptide chain. They are
located primarily on the protein surface and accordingly contain polar
and charged residues.
121
3. Tertiary structure:
the overall shape of a single protein
molecule; the spatial relationship of the secondary structures to one
another. Tertiary
structure is generally
stabilized
by
non-local
interactions, most commonly the formation of a hydrophobic core, but
also through salt bridges, hydrogen bonds, disulfide bonds, and even
122
post-translational modifications. The term "tertiary structure" is often
used as synonymous with the term fold.
The tertiary structure of a protein molecule, or of a subunit of a protein
molecule, is the arrangement of all its atoms in space, without regard
to its relationship with neighboring molecules or subunits.
The folding of the backbone upon itself to form a sphere, are called the
tertiary structure.
4. Quaternary structure:
the shape or structure that results
from the interaction of more than one protein molecule, usually called
protein subunits in this context, which function as part of the larger
assembly or protein complex.
The quaternary structure of a protein molecule is the arrangement of
its subunits in space and the ensemble of its intersubunit contacts and
interactions, without regard to the internal geometry of the subunits.
The subunits in a quaternary structure must be in non-covalent
association. Haemoglobin contains four polypeptide chains held
123
together non-covalently in a specific conformation as required for its
function.
Classes of Proteins:
Proteins can be informally divided into three main classes, which
correlate with typical tertiary structures:
1.Globular proteins:
These are small proteins,
somewhat
spherical in shape because of folding of the protein chains upon
themselves. Globular proteins are water-soluble and perform various
functions in an organism. For example, hemoglobin transports oxygen
to the cells; insulin aids in carbohydrates metabolism; antibodies
render foreign protein inactive; fibrinogen (soluble) can form insoluble
fibers that result in blood clots; and hormones carry messages
throughout the body. Examples of globular proteins are albumines,
globulines and histones.
124
2.Fibrous proteins
(structural proteins):
They
are
composed of long thread-like molecules that are tough and insoluble.
It forms skin, muscles, the walls of arteries and hair. Examples of
fibrous proteins are collagens, elastins and keratins.
3.Conjugated proteins (membrane proteins):
Proteins
connected to a non-protein moiety such as a sugar, perform various
functions throughout the body.
A common mode of action linkage
between the protein and non-protein is by a functional side chain of
the protein. For example, an acidic side chain of the protein can form
an ester with an –OH group of a sugar molecule. Examples of
conjugated proteins are nucleoproteins, mucoproteins, glycoproteins
and lipoproteins.
Almost all globular proteins are soluble and many are
enzymes. Fibrous proteins are often structural; conjugated
proteins often serve as receptors or provide channels for
polar or charged molecules to pass through the cell
membrane.
A special case of intramolecular hydrogen bonds within proteins, poorly
shielded
from
water
attack
and
hence
promoting
their
own
dehydration, are called dehydrons.
Cellular functions
The best-known role of proteins in the cell is their duty as enzymes,
which catalyze chemical reactions. Enzymes are usually highly specific
125
catalysts that accelerate only one or a few chemical reactions. Enzymes
carry out most of the reactions involved in metabolism and catabolism,
as well as DNA replication, DNA repair, and RNA synthesis. Some
enzymes act on other proteins to add or remove chemical groups in a
process
known
as
post-translational
modification.
About
4,000
reactions are known to be catalyzed by enzymes. The rate acceleration
conferred by enzymatic catalysis is often enormous - as much as 1017fold increase in rate over the un-catalyzed reaction in the case of
orotate decarboxylase (78 million years without the enzyme, 18
milliseconds with the enzyme).
The molecules bound and acted upon by enzymes are known as
substrates. Although enzymes can consist of hundreds of amino acids,
it is usually only a small fraction of the residues that come in contact
with the substrate, and an even smaller fraction - 3-4 residues on
average - that are directly involved in catalysis. The region of the
enzyme that binds the substrate and contains the catalytic residues is
known as the active site.
Protein Denaturation
Protein denaturation has been defined in several ways, for example as
a change in solubility or by simultaneous changes in chemical, physical
and biological properties under some standard reference set of
conditions. These changes in physical, and to a lesser extent chemical
properties are manifestations of configurational changes taking place
in the polypeptide chains.
The denaturation process presumably involves an unfolding or at least
an alteration in the nature of the folded structure. Most denaturation
126
changes consist of changes in secondary bonds: ion-dipole, hydrogen
and Van der Waals, and in the rotational positions about single bonds
which are controlled by the secondary bond structure.
The term denaturation denotes the response of the native protein to
heat, acid, alkali, and a variety of other chemical and physical agents
which cause marked changes in the protein structure. Rice et al.
(1958) suggested denaturation to mean a class of reactions which lead
to changes in the structure of the macromolecule with no change in
molecular weight.
Timasheff and Gibbs (1957), pointed out that the approaches used to
define the concept of denaturation can be classified into two types:

molecular, in terms of actual structural changes taking place on
the molecule, and

operational, in terms of changes in measurable properties.
The operational approach to denaturation has the advantage of being
purely phenomenological, but it cannot lead to a precise definition,
127
since the concept of property, even restricted to measurable property,
is itself without finite boundary. On the other hand, the molecular point
of view, although still involves a few assumptions despite the
important advances in investigations of protein structure, will allow us
to reach a definition which is very convenient, owing to its general
validity. Whatever it is, changes can be quantitatively described by
comparison with the native state.
The denaturation process can be achieved by any one of the following
methods:

Increasing temperature.

Changing pH.

Using denaturants (i.e. urea, guanidine hydrochloride, betamercaptoethanol, dithiothreitol).

Using
inorganic
salts
(i.e
lithium
bromide,
potassium
thiocyanate, sodium iodide).

Using organic solvents and (i.e. formamide, dimethylformamide,
dichloro- and trichloroacetic acids and their salts).

Using detergents (i.e. sodium dodecyl sulphate).

High pressure.

Ultrasonic homogenization.
128
Enzymes
Enzymes are biological catalysts responsible for supporting almost all
of the chemical reactions that maintain animal homeostasis.
Because of their role in maintaining life processes, the assay and
pharmacological regulation of enzymes have become key elements in
clinical diagnosis and therapeutics.
The macromolecular components of almost all enzymes are composed
of protein, except for a class of RNA modifying catalysts known as
ribozymes. Ribozymes are molecules of ribonucleic acid that catalyze
reactions on the phosphodiester bond of other RNAs.
Enzymes are found in all tissues and fluids of the body. Almost every
significant life process is dependent on enzyme activity.

Intracellular enzymes catalyze the reactions of metabolic
pathways.

Plasma membrane enzymes regulate catalysis within cells in
response to extracellular signals.

Circulatory system enzymes are responsible for regulating the
clotting of blood.
Enzyme Classifications
Traditionally, enzymes were simply assigned names by the investigator
who discovered the enzyme. As knowledge expanded, systems of
enzyme classification became more comprehensive and complex.
Currently enzymes are grouped into six functional classes by the
International Union of Biochemists (I.U.B.).
129
The enzyme's name is comprised of the names of:

The substrate(s),

The product(s) and

The enzyme's functional class.
In the enzyme acetyl choline esterase for example, It catalyzes the
breakdown of the neurotransmitter acetylcholine at several types of
synapses as well as at the neuromuscular junction — the specialized
synapse that triggers the contraction of skeletal muscle.
One molecule of acetylcholinesterase breaks down 25,000 molecules of
acetylcholine each second. This speed makes possible the rapid
"resetting" of the synapse for transmission of another nerve impulse.

The substrate of this enzyme is acetyl choline.

The products are acetate and choline base.
130

The enzyme functional clase is esterase because it is hydrolyze
the ester bond in the acetyl choline.
Classification of Enzymes
Classification of enzymes- More than 2000 different enzymes are
currently known. The commonly used names for most enzymes
describe the type of reaction catalyzed, followed by the suffix -ase. For
example,
dehydrogenases
hydrolyze proteins, and
remove
isomerases
hydrogen
atoms,
proteases
catalyze rearrangements in
configuration. Modifiers may precede the name to indicate the
substrate (xanthine oxidase), the source of the enzyme (pancreatic
ribonuclease), its regulation (hormone-sensitive lipase) etc.
To address ambiguities, the International Union of Biochemists (IUB)
developed an unambiguous system of enzyme nomenclature in which
each enzyme has a unique name and code number that identify the
type of reaction catalyzed and the substrates involved. Enzymes are
grouped into six classes:
1) The oxidoreductases (class 1) catalyze the transfer of reducing
equivalents(Hydrogen
and
electrons)from
one
redox
system
to
another.
2) The transferases (class 2) catalyze the transfer of other groups from
one molecule to another. Oxidoreductases and transferases generally
require coenzymes
3) The hydrolases (class 3) hydrolases cause cleavage of bond using
water
4) Lyases (class 4, often also referred to as“synthases”) catalyze
reactions involving either the cleavage or formation of chemical bonds,
131
with double bonds either arising or disappearing.(See figure- reversible
reaction is shown). Cleavage of bond does not require water.
5) The isomerases (class 5) move groups within a molecule, without
changing the gross composition of the substrate.
6) The ligation reactions catalyzed by ligases (“synthetases,” class 6)
are energy-dependent and are therefore always coupled to the
hydrolysis of nucleoside triphosphates(See figure)
Each enzyme is entered in the Enzyme Catalogue with a four-digit
Enzyme Commission number (EC number). The first digit indicates
membership of one of the six major classes. The next two indicate
subclasses and subsubclasses. The last digit indicates where the
enzyme belongs in the subsubclass.
For example, The IUB name of hexokinase is ATP:D-hexose 6phosphotransferase E.C. 2.7.1.1. This name identifies hexokinase as a
member of class 2 (transferases), subclass 7 (transfer of a phosphoryl
group), sub-subclass 1 (alcohol is the phosphoryl acceptor), and
“hexose-6″ indicates that the alcohol phosphorylated is on carbon six
of a hexose. However, it is still called as hexokinase.
132
Figure- Showing the classification of enzymes with
examples of each class of enzymes:
Enzymes are also classified on the basis of their
composition:
1. Simple enzymes:
They are composed wholly of protein.
133
2. Complex enzymes:
They are composed of protein plus non-protein component (a
relatively small organic molecule).
Complex enzymes are also known as HOLOENZYMES.
In this
terminology
the
protein component
is
known as the
APOENZYME.
Non-protein component is known as the COENZYME or PROSTHETIC
GROUP.
When
the
binding
between
the
apoenzyme
and
non-protein
components is non-covalent, the small organic molecule is called
coenzyme. When the binding between the apoenzyme and non-protein
components is covalent, the small organic molecule is called Prosthetic
group.
Many prosthetic groups and coenzymes are water-soluble derivatives
of vitamins.
It should be noted that the main clinical symptoms of dietary vitamin
insufficiency generally arise from the malfunction of enzymes , which
lack
sufficient
cofactors
derived
from
vitamins
to
maintain
homeostasis.
The non-protein component of an enzyme may be as simple as a metal
ion or as complex as a small non-protein organic molecule.
Enzymes that require a metal in their composition are known as
METALLOENZYMES if they bind and retain their metal atom(s) under all
conditions with very high affinity.
While those which have a lower
affinity for metal ion, but still require the metal ion for activity, are
known as METAL-ACTIVATED ENZYMES.
134
Role of Coenzymes
The functional role of coenzymes is to act as transporters of chemical
groups from one reactant to another.
The chemical groups carried can be as simple as the hydride ion (H+ +
2e-) carried by NAD or the mole of hydrogen carried by FAD; or they
can be even more complex than the amine (-NH2) carried by pyridoxal
phosphate.
Since coenzymes are chemically changed as a consequence of enzyme
action, it is often useful to consider coenzymes to be a special class of
substrates, or second substrates, which are common to many different
holoenzymes.
In all cases, the coenzymes donate the carried chemical grouping to an
acceptor molecule and are thus regenerated to their original form. This
regeneration of coenzyme and holoenzyme fulfills the definition of an
enzyme as a chemical catalyst, since (unlike the usual substrates,
which are used up during the course of a reaction) coenzymes are
generally regenerated.
Enzyme Relative to Substrate Type
Although enzymes are highly specific for the kind of reaction they
catalyze, the same is not always true of substrates they attack.
For example,
Succinic dehydrogenase (SDH) always catalyzes an oxidation reduction
reaction and its substrate is succinic acid.
135
Alcohol dehydrogenase (ADH) also catalyzes oxidation-reduction
reactions but attacks a number of different alcohols, ranging from
methanol to butanol.
Generally, enzymes having broad substrate specificity are most active
against
one
particular
substrate.
In
the
case
of
alcohol
dehydrogenase, ethanol is the preferred substrate.
Enzymes also are generally specific for a particular steric configuration
(optical isomer) of a substrate.
Enzymes that attack D-sugars will not attack the corresponding
L-
isomer.
Enzymes that act on L-amino acids will not employ the corresponding
D-optical isomer as a substrate.
The enzymes known as racemases provide a striking exception to these
generalities; in fact, the role of racemases is to convert D-isomers to Lisomers and vice versa. Thus racemases attack both D and L forms of
their substrate.
As enzymes have a more or less broad range of substrate specificity, it
follows that a given substrate may be acted on by a number of
different enzymes, each of which uses the same substrate(s) and
produces the same product(s). The individual members of a set of
enzymes sharing such characteristics are known as ISOZYMES.
The best studied set of isozymes is the lactate dehydrogenase (LDH)
system.
136
LDH is a tetrameric enzyme composed of all possible arrangements of
two different protein subunits. These subunits combine in various
combinations leading to 5 distinct isozymes.
ENZYME-SUBSTRATE INTERACTIONS
The favored model of enzyme substrate interaction is known as the
induced fit model.
This model proposes that the initial interaction between enzyme and
substrate is relatively weak, but that these weak interactions rapidly
induce conformational changes in the enzyme that strengthen binding
and bring CATALYTIC SITES close to substrate bonds to be altered.
Enzymes as Biological Catalysts
In cells and organisms most reactions are catalyzed by enzymes, which
are regenerated during the course of a reaction. These biological
catalysts are physiologically important because they speed up the rates
of reactions that would otherwise be too slow to support life.
Enzymes increase reaction rates sometimes by as much as one million
fold, but more typically by about one thousand fold. Catalysts speed up
the forward and reverse reactions proportionately so that, although the
magnitude of the rate constants of the forward and reverse reactions is
are increased, the ratio of the rate constants remains the same in the
presence or absence of enzyme.
137
Enzymes increase reaction rates by decreasing the amount of energy
required to form a complex of reactants that is competent to produce
reaction products. This complex is known as the activated state or
transition state complex for the reaction.
Michaelis-Menton Kinetics
In
typical
enzyme-catalyzed
reactions,
reactant
and
product
concentrations are usually hundreds or thousands of times greater
than the enzyme concentration. Consequently, each enzyme molecule
catalyzes the conversion to product of many reactant molecules.
In
biochemical
reactions,
reactants
are
commonly
known
as
substrates. The catalytic event that converts substrate to product
involves the formation of a transition state, and it occurs most easily at
a specific binding site on the enzyme. This site, called the catalytic site
of the enzyme, has been evolutionarily structured to provide specific,
high-affinity binding of substrate(s) and to provide an environment
that favors the catalytic events.
The complex that forms when substrate(s) and enzyme combined, is
called the enzyme substrate (ES) complex. Reaction products arise
when the ES complex breaks down releasing free enzyme.
Between the binding of substrate to enzyme, and the reappearance of
free enzyme and product, a series of complex events must take place.
At a minimum an ES complex must be formed; this complex must pass
to the transition state (ES*); and the transition state complex must
advance to an enzyme product complex (EP). The latter is finally
138
competent to dissociate to product and free enzyme. The series of
events can be shown thus:
E+S <--> EScomplex<--> ES*complex<--> EPcomplex<--> E + P
The kinetics of simple reactions like that above were first characterized
by biochemists Michaelis and Menten. The concepts underlying their
analysis of enzyme kinetics continue to provide the cornerstone for
understanding metabolism today, and for the development and clinical
use of drugs aimed at selectively altering rate constants and interfering
with the progress of disease states.
The Michaelis-Menten equation is a quantitative description of the
relationship among the rate of an enzyme- catalyzed reaction [v1], the
concentration of substrate [S] and two constants, Vmax and Km (which
are set by the particular equation).
The symbols used in the Michaelis-Menton equation refer to the
reaction
rate
[v1],
maximum
reaction
rate
(Vmax),
substrate
concentration [S] and the Michaelis-Menton constant (Km).
The Michaelis-Menten equation can be used to demonstrate that at the
substrate concentration that produces exactly half of the maximum
reaction rate, i.e., 1/2 Vmax , the substrate concentration is numerically
equal to Km.
139
This fact provides a simple yet powerful bioanalytical tool that has
been used to characterize both normal and altered enzymes, such as
those that produce the symptoms of genetic diseases.
Rearranging the Michaelis-Menton equation leads to:
From this equation it should be apparent that when the substrate
concentration is half that required to support the maximum rate of
reaction, the observed rate, v1, will, be equal to Vmax divided by 2;
in other words,
v1 = [Vmax/2].
At this substrate concentration Vmax/v1 will be exactly equal to 2, with
the result that:
Km =[S])2-1) = [S]
The latter is an algebraic statement of the fact that, for enzymes of the
Michaelis-Menten type, when the observed reaction rate is half of the
maximum possible reaction rate, the substrate concentration (S) is
numerically equal to the Michaelis-Menten constant (Km) . In this
derivation, the units of Km are those used to specify the concentration
of S, usually Molarity.
140
Plotting of
substrate
concentration
versus
reaction
velocity
in
Michaelis-Menten equation:
The key features of the plot are marked by points A, B and C. At high
substrate concentrations the rate represented by point C the rate of
the reaction is almost equal to Vmax, and the difference in rate at
nearby concentrations of substrate is almost negligible.
If the Michaelis-Menten plot is extrapolated to infinitely high substrate
concentrations, the extrapolated rate is equal to Vmax. When the
reaction rate becomes independent of substrate concentration, or
nearly so, the rate is said to be zero order.
141
The
very
small
differences
in
reaction
velocity
at
substrate
concentrations around point C (near Vmax) reflect the fact that at these
concentrations almost all of the enzyme molecules are bound to
substrate and the rate is virtually independent of substrate, hence zero
order.
At lower substrate concentrations, such as at points A and B, the lower
reaction velocities indicate that at any moment only a portion of the
enzyme molecules are bound to the substrate. In fact, at the substrate
concentration denoted by point B, exactly half the enzyme molecules
are in an EScomplex at any instant and the rate is exactly one half of Vmax.
At substrate concentrations near point A the rate appears to be directly
proportional to substrate concentration, and the reaction rate is said to
be first order.
Inhibition of Enzyme Catalyzed Reactions
To avoid dealing with curvilinear plots of enzyme catalyzed reactions,
biochemists Lineweaver and Burk introduced an analysis of enzyme
kinetics based on the following rearrangement of the Michaelis-Menten
equation:
Take the inverse:
1/v1 = Km /Vmax[S]
+
1/Vmax
142
Plots of 1/v1 versus 1/[S] yield straight lines having a slope of Km/Vmax
and an intercept on the ordinate at 1/Vmax.
A Lineweaver-Burk Plot
Lineweaver-Burk transformation of the Michaelis-Menton equation is
useful in the analysis of enzyme inhibition.
Since most clinical drug therapy is based on inhibiting the activity of
enzymes, analysis of enzyme reactions using the tools described above
has been fundamental to the modern design of pharmaceuticals.
Enzyme inhibitors fall into two broad classes:
1. Inhibitors causing irreversible inactivation of enzymes.
2. Inhibitors whose inhibitory effects can be reversed.
3.
Irreversible Inhibitors:
143
They cause an inactivating, covalent modification of enzyme structure.
Cyanide is a classic example of an irreversible enzyme inhibitor by
covalently binding mitochondrial cytochrome oxidase, it inhibits all the
reactions associated with electron transport.
The kinetic effect of irreversible inhibitors is to decrease the
concentration of active enzyme, thus decreasing the maximum possible
concentration of EScomplex . Since the limiting enzyme reaction rate is
often k2[ES], it is clear that under these circumstances the reduction of
enzyme concentration will lead to decreased reaction rates.
Note that when enzymes in cells are only partially inhibited by
irreversible inhibitors, the remaining unmodified enzyme molecules are
not distinguishable from those in untreated cells; in particular, they
have the same turnover number and the same Km. Turnover number,
related to Vmax, is defined as the maximum number of moles of
substrate that can be converted to product per mole of catalytic site
per second.
Irreversible inhibitors are usually considered to be poisons and are
generally unsuitable for therapeutic purposes.
Reversible inhibitors:
They can be divided into three categories:
1. Competitive inhibitors.
2. Noncompetitive inhibitors.
3. Uncompetitive inhibitors.
144
Inhibitor
Type
Binding Site on Enzyme

Kinetic effect
Specifically at the catalytic
site.
Competitive

Inhibitor

It competes with substrate

Vmax is unchanged.
for binding.

Km

Km appears unaltered.

Vmax
is increased.
Inhibition is reversible by
substrate.

Binds E or ES complex
other than at the catalytic
site.
Noncompetitive

Inhibitor

Substrate
binding
is
decreased
unaltered, but ESI complex
proportionately
cannot form products.
inhibitor conc.
Inhibition
cannot
to
be
reversed by substrate.

Binds only to ES complexes
at locations other than the
catalytic site.
Uncompetitive

Substrate binding modifies

enzyme structure, making
Inhibitor
inhibitor-
binding
site
cannot
be
available.

Inhibition
reversed by substrate.
145
Apparent
decreased.

Km is decreased.
Vmax
When the reversible inhibitor concentration drops, enzyme activity is
regenerated. Usually these inhibitors bind to enzymes by non-covalent
forces and the inhibitor maintains a reversible equilibrium with the
enzyme.
The equilibrium constant for the dissociation of enzyme inhibitor
complexes is known as KI:
KI = [E] [I] / [EI complex]
The importance of KI is that in all enzyme reactions where substrate,
inhibitor and enzyme interact, the normal Km and or Vmax for substrate
enzyme interaction appear to be altered. These changes are a
consequence of the influence of KI on the overall rate equation for the
reaction. The effects of KI are best observed in Lineweaver-Burk plots.
Probably
the best
known reversible inhibitors are
competitive
inhibitors, which always bind at the catalytic or active site of the
enzyme. Most drugs that alter enzyme activity are of this type.
Competitive inhibitors are especially attractive as clinical modulators of
enzyme activity because they offer two routes for the reversal of
enzyme inhibition, while other reversible inhibitors offer only one.
First, as with
all
kinds
of
reversible inhibitors,
a
decreasing
concentration of the inhibitor reverses the equilibrium regenerating
active free enzyme.
Second, since substrate and competitive inhibitors both bind at the
same site they compete with one another for binding
146
Raising the concentration of substrate (S), while holding the
concentration of inhibitor constant, provides the second route for
reversal of competitive inhibition. The greater the proportion of
substrate, the greater the proportion of enzyme present in competent
ES complexes.
As noted earlier, high concentrations of substrate can displace virtually
all competitive inhibitor bound to active sites. Thus, it is apparent that
Vmax should be unchanged by competitive inhibitors.
147
Lineweaver-Burk Plots of Inhibited Enzymes
148
4. NUCLEIC ACID
Nucleic acids were found to be major components of chromosomes,
small gene-carrying bodies in the nuclei of complex cells. Elemental
analysis of nucleic acids showed the presence of phosphorus, in
addition to the usual C, H, N & O. Unlike proteins, nucleic acids
contained no sulfur. Complete hydrolysis of chromosomal nucleic acids
gave inorganic phosphate, 2-deoxyribose (a previously unknown
sugar) and four different heterocyclic bases (shown in the following
diagram). To reflect the unusual sugar component, chromosomal
nucleic acids are called deoxyribonucleic acids, abbreviated DNA.
Analogous nucleic acids in which the sugar component is ribose are
termed ribonucleic acids, abbreviated RNA. The acidic character of the
nucleic acids was attributed to the phosphoric acid moiety.
149
Chemical structure
The term "nucleic acid" is the generic name for a family of biopolymers,
named for their role in the cell nucleus. The monomers from which
nucleic acids are constructed are called nucleotides.
Each nucleotide consists of three components:

Nitrogenous heterocyclic base, which is either a purine or a
pyrimidine.

Pentose sugar.

Phosphate group.
Nucleic acid types differ in the structure of the sugar in their
nucleotides - DNA contains 2-deoxyriboses while RNA contains ribose
(where the only difference is the presence of a hydroxyl group). Also,
the nitrogenous bases found in the two nucleic acid types are different:
adenine, cytosine, and guanine are found in both RNA and DNA, while
thymine only occurs in DNA and uracil only occurs in RNA.
Types of nucleic acids
Ribonucleic acid
Ribonucleic acid, or RNA, is a nucleic acid polymer consisting of
nucleotide monomers, which plays several important roles in the
processes of translating genetic information from deoxyribonucleic
acid (DNA) into proteins. RNA acts as a messenger between DNA and
the protein synthesis complexes known as ribosomes, forms vital
portions of ribosomes, and serves as an essential carrier molecule for
amino acids to be used in protein synthesis.
150
Deoxyribonucleic acid
Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic
instructions used in the development and functioning of all known
living organisms. The main role of DNA molecules is the long-term
storage of information and DNA is often compared to a set of
blueprints, since it contains the instructions needed to construct other
components of cells, such as proteins and RNA molecules. The DNA
segments that carry this genetic information are called genes, but
other DNA sequences have structural purposes, or are involved in
regulating the use of this genetic information.
151
The two monocyclic bases shown here are classified as pyrimidines,
and the two bicyclic bases are purines. Each has at least one N-H site
at which an organic substituent may be attached. They are all
polyfunctional bases, and may exist in tautomeric forms.
The Chemical Nature of DNA
The polymeric structure of DNA may be described in terms of
monomeric
units
of
increasing
complexity.
Condensation
polymerization of these leads to the DNA formulation outlined above.
Finally, a 5'- monophosphate ester, called a nucleotide may be drawn
as a single monomer unit. Since a monophosphate ester of this kind is
a strong acid, it will be fully ionized at the usual physiological pH
(ca.7.4). DNA components are given by selective hydrolysis of DNA
through the action of nuclease enzymes. Anhydride-like di- and triphosphate nucleotides have been identified as important energy
carriers in biochemical reactions, the most common being ATP
(adenosine 5'-triphosphate).
152
153
A complete structural representation of a segment of the DNA polymer
formed from 5'-nucleotides. Several important characteristics of this
formula should be noted.
• First, the remaining P-OH function is quite acidic and is
completely ionized in biological systems.
• Second, the polymer chain is structurally directed. One end (5')
is different from the other (3').
• Third, although this appears to be a relatively simple polymer,
the possible permutations of the four nucleosides in the chain
become very large as the chain lengthens.
• Fourth, the DNA polymer is much larger than originally
believed. Molecular weights for the DNA from multicellular
organisms are commonly 109 or greater.
Nucleic acid components
Nucleobases
Nucleobases are heterocyclic aromatic organic compounds containing
nitrogen atoms. Nucleobases are the parts of RNA and DNA involved in
base
pairing.
Cytosine,
guanine,
adenine,
thymine
are
found
predominantly in DNA, while in RNA uracil replaces thymine. These are
abbreviated as C, G, A, T, U, respectively.
Nucleobases are complementary, and when forming base pairs, must
always join accordingly: cytosine-guanine, adenine-thymine (adenineuracil when RNA). The strength of the interaction between cytosine
and guanine is stronger than between adenine and thymine because
the former pair has three hydrogen bonds joining them while the latter
pair have only two. Thus, the higher the GC content of double-stranded
DNA, the more stable the molecule and the higher the melting
temperature.
154
Two main nucleobase classes exist, named for the molecule which
forms their skeleton. These are the double-ringed purines and singleringed pyrimidines. Adenine and guanine are purines (abbreviated as
R), while cytosine, thymine, and uracil are all pyrimidines (abbreviated
as Y).
Hypoxanthine and xanthine are mutant forms of adenine and guanine,
respectively, created through mutagen presence, through deamination
(replacement of the amine-group with a hydroxyl-group). These are
abbreviated HX and X.
Nucleosides
Nucleosides are glycosylamines made by attaching a nucleobase (often
referred to simply as bases) to a ribose or deoxyribose (sugar) ring. In
short, a nucleoside is a base linked to sugar. The names derive from the
nucleobase names. The nucleosides commonly occurring in DNA and
RNA include cytidine, uridine, adenosine, guanosine and thymidine.
When a phosphate is added to a nucleoside (by phosphorylated by a
specific
kinase
enzyme),
a
nucleotide
is
produced.
Nucleoside
analogues, such as acyclovir, are used as antiviral agents.
Nucleotides and deoxynucleotides
A nucleotide consists of a nucleoside and one or more phosphate
groups. Nucleotides are the monomers of RNA and DNA, as well as
forming the structural units of several important cofactors - CoA, flavin
adenine dinucleotide, flavin mononucleotide, adenosine triphosphate
and
nicotinamide
adenine
dinucleotide
phosphate.
In
the
cell
nucleotides play important roles in metabolism, and signaling.
Nucleotides are named after the nucleoside on which they are based, in
conjunction with the number of phosphates they contain, for example:
155

Adenine bonded to ribose forms the
nucleoside adenosine.

Adenosine bonded to a phosphate forms
adenosine monophosphate.
As phosphates are added, adenosine diphosphate and adenosine
triphosphate are formed, in sequence.
156
5. VITAMINS & MINERALS
Vitamins are organic substances (made by plants or animals), minerals
are inorganic elements that come from the earth; soil and water and
are absorbed by plants. Animals and humans absorb minerals from the
plants they eat. Vitamins and minerals are nutrients that your body
needs to grow and develop normally.
Vitamins and minerals, have a unique role to play in maintaining your
health. For example Vitamin D helps your body absorb the amount of
calcium (a mineral) it needs to form strong bones. A deficiency in
vitamin D can result in a disease called rickets (softening of the bones
caused by the bodies inability to absorb the mineral calcium.) The body
cannot produce calcium; therefore, it must be absorbed through our
food. Other minerals like chromium, copper, iodine, iron, selenium, and
zinc are called trace minerals because you only need very small
amounts of them each day. The best way to get enough vitamins is to
eat a balanced diet with a variety of foods. You can usually get all your
vitamins from the foods you eat.
157
Vitamins Hang Out in Water and Fat
There are two types of vitamins: fat soluble and water soluble.
When you eat foods that contain fat-soluble vitamins, the vitamins are
stored in the fat tissues in your body and in your liver. They wait
around in your body fat until your body needs them.
Fat-soluble vitamins are happy to stay stored in your body for awhile —
some stay for a few days, some for up to 6 months! Then, when it's
time for them to be used, special carriers in your body take them to
where they're needed. Vitamins A, D, E, and K are all fat-soluble
vitamins.
Water-soluble vitamins are different. When you eat foods that have
water-soluble vitamins, the vitamins don't get stored as much in your
body. Instead, they travel through your bloodstream. Whatever your
body doesn't use comes out when you urinate (pee).
So these kinds of vitamins need to be replaced often because they
don't stick around! This crowd of vitamins includes vitamin C and the
big group of B vitamins — B1 (thiamin), B2 (riboflavin), niacin, B6
(pyridoxine), folic acid, B12 (cobalamine), biotin, and pantothenic acid.
Vitamins Feed Your Needs
Your body is one powerful machine, capable of doing all sorts of things
by itself. But one thing it can't do is make vitamins. That's where food
comes in. Your body is able to get the vitamins it needs from the foods
you eat because different foods contain different vitamins. The key is
to eat different foods to get an assortment of vitamins. Though some
kids take a daily vitamin, most kids don't need one if they're eating a
variety of healthy foods.
158
VITAMINS & COENZYMES
Vitamins are organic molecules that function in a wide variety of
capacities within the body. The most prominent function is as cofactors
for enzymatic reactions. They generally cannot be synthesized by
mammalian cells and therefore, must be supplied in the diet.
The vitamins are of two types:
1. Water Soluble Vitamins
2. Fat Soluble Vitamins
Thiamin (B1)
Riboflavin (B2)
Niacin (B3)
Vitamin A
Pantothenic Acid (B5)
Vitamin D
Pyridoxine (B6)
Vitamin E
Biotin
Vitamin K
Cobalamin (B12)
Folic Acid
Ascorbic Acid
159
Thiamin (Vitamin B1)
Thiamin is also known as vitamin B1 . Thiamin is rapidly converted to
its active form, thiamin pyrophosphate, TPP, in the brain and liver by a
specific enzymes, thiamin diphosphotransferase.
Thiamin pyrophosphate (TPP)
160
TPP is necessary as a cofactor for the pyruvate and ketoglutarate
dehydrogenase catalyzed reactions as well as the transketolase
catalyzed reactions of the pentose phosphate pathway.
The dietary requirement for thiamin is proportional to the caloric
intake of the diet and ranges from 1.0 - 1.5 mg/day for normal adults.
The severe thiamin deficiency disease known as Beriberi ‫مرض الهزال‬
‫والضعف‬, is the result of a diet that is carbohydrate rich and thiamin
deficient.
Riboflavin (Vitamin B2)
Riboflavin is the precursor for the coenzymes, flavin mononucleotide
(FMN) and flavin adenine dinucleotide (FAD).
The enzymes that require FMN or FAD as cofactors are termed
flavoproteins. Several flavoproteins also contain metal ions and are
termed metalloflavoproteins.
161
Both classes of enzymes flavoproteins and metalloflavoproteins are
involved
in
a
wide
range
of
redox
reactions,
e.g.
succinate
dehydrogenase and xanthine oxidase.
During
the course of the enzymatic
reactions involving the
flavoproteins, the reduced forms of FMN and FAD are formed, FMNH2
and FADH2, respectively.
The normal daily requirement for riboflavin is 1.2 - 1.7 mg/day for
normal adults.
Structure
of
nitrogens 1 & 5 carry hydrogens in FADH2
FAD
Riboflavin is present in eggs, milk, meat and cereals.
Riboflavin
decomposes
when
exposed
to
visible
light.
This
characteristic can lead to riboflavin deficiencies in newborns treated
162
for hyperbilirubinemia (Increase in bilirubin in blood, bilirubin is a bile
pigment which is a degradation product of heme)) by phototherapy.
Vitamin B3
Niacin (nicotinamide & nicotinic acid)
Nicotinamide
Nicotinic Acid
Niacin (nicotinic acid and nicotinamide) is also known as vitamin B3.
Both nicotinic acid and nicotinamide can serve as the dietary source of
vitamin B3.
Niacin is required for the synthesis of the active forms of vitamin B 3,
nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine
dinucleotide phosphate (NADP+). Both NAD+ and NADP+ function as
cofactors for numerous dehydrogenase, e.g., lactate and malate
dehydrogenases.
163
Structure
NADH
of
is
shown
in
NAD+
the
box
insert.
The -OH phosphorylated in NADP+ is indicated by the red arrow.
Niacin is not a true vitamin in the strictest definition since it can be
derived from the amino acid tryptophan.
Also, synthesis of niacin from tryptophan requires vitamins B1, B2 and
B6 .
The recommended daily requirement for niacin is 13 - 19 niacin
equivalents (NE) per day for a normal adult. One NE is equivalent to 1
mg of free niacin).
The severe symptoms, depression, dermatitis and diarrhea, are
associated with the condition known as pellagra )‫داء ( مرض جلدي‬
‫البالجرا‬
164
Nicotinic
acid
(but
not
nicotinamide)
when
administered
in
pharmacological doses of 2 - 4 g/day lowers plasma cholesterol levels
and
has
been
shown
to
be
a
useful
therapeutic
for
hypercholesterolemia.
The major action of nicotinic acid in this capacity is a reduction in fatty
acid mobilization from adipose tissue.
Although nicotinic acid therapy lowers blood cholesterol it also causes
a depletion of glycogen stores and fat reserves in skeletal and cardiac
muscle.
Additionally, there is an elevation in blood glucose and uric acid
production.
Pantothenic Acid (Vitamin B5)
Pantothenic
acid
is
formed
from
alanine
and
pantoic
acid.
Pantothenate is required for synthesis of coenzyme A, CoA and is a
component of the acyl carrier protein (ACP) domain of fatty acid
synthase.
165
Coenzyme A
Pantothenate
is,
therefore,
required
for
the
metabolism
of
carbohydrate via the TCA cycle and all fats and proteins. At least 70
enzymes have been identified as requiring CoA or ACP derivatives for
their function.
Deficiency of pantothenic acid is extremely rare due to its widespread
distribution in whole grain cereals, legumes and meat.
Symptoms of pantothenate deficiency are difficult to assess since they
are subtle and resemble those of other B vitamin deficiencies.
166
Vitamin B6
Pyridoxine
Pyridoxal
Pyridoxamine
Pyridoxal, pyridoxamine and pyridoxine are collectively known as
vitamin B6. All three compounds are efficiently converted to the
biologically active form of vitamin B6, pyridoxal phosphate.
This conversion is catalyzed by the ATP requiring enzyme, pyridoxal
kinase.
Pyridoxal Phosphate
Pyridoxal phosphate functions as a cofactor in enzymes involved in
transamination reactions required for the synthesis and catabolism of
the amino acids as well as in glycogenolysis as a cofactor for glycogen
phosphorylase. The requirement for vitamin B6 in the diet is
proportional to the level of protein consumption ranging from 1.4 - 2.0
167
mg/day for a normal adult. During pregnancy and lactation the
requirement for vitamin B6 increases approximately 0.6 mg/day.
Deficiencies of vitamin B6 are rare and usually are related to an overall
deficiency of all the B-complex vitamins.
Biotin
Biotin is the cofactor required of enzymes that are involved in
carboxylation reactions, e.g. acetyl-CoA carboxylase and pyruvate
carboxylase.
Biotin is found in numerous foods and also is synthesized by intestinal
bacteria and as such deficiencies of the vitamin are rare.
Deficiencies are generally seen only after long antibiotic therapies
which deplete the intestinal fauna or following excessive consumption
of raw eggs. The latter is due to the affinity of the egg white protein,
avidin, for biotin preventing intestinal absorption of the biotin.
168
Cobalamin (Vitamin B12)
Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin
ring) and a cobalt ion in the center.
Vitamin B12 is synthesized exclusively by microorganisms and is found
in the liver of animals bound to protein as methycobalamin or 5'-deoxy
adenosyl cobalamin.
The vitamin must be hydrolyzed from protein in order to be active.
Hydrolysis occurs in the stomach by gastric acids or the intestines by
trypsin digestion following consumption of animal meat. The vitamin is
then bound by intrinsic factor, a protein secreted by parietal cells ‫الخاليا‬
‫ الجدارية‬of the stomach, and carried to the ileum ‫ المعي اللفائفي‬where
it is absorbed.
Following absorption the vitamin is transported to the liver in the blood
bound to transcobalamin II.
There are only two clinically significant reactions in the body that
require vitamin B12 as a cofactor:
1. During the conversion of methylmalonyl-CoA to succinyl-CoA.
2. For catalysis of the conversion of homocysteine to methionine.
169
Cyanocobalamin
Pernicious anemia ‫ فقر الدم الخبيث‬is a megaloblastic anemia resulting
from vitamin B12 deficiency that develops as a result a lack of intrinsic
factor in the stomach leading to malabsorption of the vitamin.
170
Folic Acid
Folic Acid
Folic acid is obtained primarily from yeasts and leafy vegetables as well
as animal liver.
Folic acid is reduced within cells (principally the liver where it is
stored) to tetrahydrofolate (THF). The function of THF derivatives is to
carry and transfer various forms of one carbon units during
biosynthetic reactions. The one carbon units are either methyl,
methylene, methenyl, formyl or formimino groups.
171
These one carbon transfer reactions are required in the biosynthesis of
serine, methionine, glycine, choline and the purine nucleotides and
dTMP.
The most pronounced effect of folate deficiency on cellular processes is
upon DNA synthesis. The result is MEGALOBLASTIC ANEMIA as for
vitamin B12 deficiency. The inability to synthesize DNA during
erythrocyte maturation leads to abnormally large erythrocytes termed
MACROCYTIC ANEMIA.
172
Ascorbic Acid (Vitamin C)
Ascorbic acid is derived from glucose via the uronic acid pathway.
The main function of ascorbate is as a reducing agent in a number of
different reactions.
Vitamin C has the potential to reduce cytochromes A and C of the
respiratory chain as well as molecular oxygen.
The most important reaction requiring ascorbate as a cofactor is the
hydroxylation of proline residues in collagen.
Vitamin C is, therefore, required for the maintenance of normal
connective tissue as well as for wound healing since synthesis of
connective tissue is the first event in wound tissue remodeling.
Vitamin C also is necessary for bone remodeling due to the presence of
collagen in the organic matrix of bones.
Several other metabolic reactions require vitamin C as a cofactor.
These include the catabolism of tyrosine and the synthesis of
epinephrine from tyrosine and the synthesis of the bile acids. It is also
believed that vitamin C is involved in the process of steroidogenesis
since the adrenal cortex contains high levels of vitamin C which are
depleted upon adrenocorticotropic hormone (ACTH) stimulation of the
gland.
173
The disease SCURVY
)‫ (داء االسقربوط تورم اللثة ونزف الدم منها‬due to
the role of the vitamin in the post-translational modification of
collagens. ‫المادة البروتينية في النسيج والعظم‬
Vitamin C is readily absorbed and so the primary cause of vitamin C
deficiency is poor diet and/or an increased requirement.
Soluble vitamins in lipid
Vitamin A
Vitamin A consists of three biologically active molecules, retinol, retinal
and retinoic acid.
Retinal
Retinol
Retinoic Acid
174
Each of these compounds is derived from the plant precursor molecule,
β-carotene (a member of a family of molecules known as carotenoids).
β-carotene, which consists of two molecules of retinal linked at their
aldehyde ends, is also referred to as the provitamin form of vitamin A.
Ingested β -carotene is cleaved in the lumen ‫ تجويف‬of the intestine by
β -carotene dioxygenase to yield retinal.
Retinal is reduced to retinol. Retinol is esterified to palmitic acid and
delivered to the blood.
The earliest symptoms of vitamin A deficiency are night blindness.
Prolonged lack of vitamin A leads to deterioration of the eye tissue
through progressive keratinization of the cornea, a condition known as
xerophthalmia. ‫جفاف العين‬
Beta-carotene is a very effective antioxidant and is suspected to reduce
the risk of cancers known to be initiated by the production of free
radicals.
Of particular interest is the potential benefit of increased β-carotene
intake to reduce the risk of lung cancer in smokers. However, caution
needs to be taken when increasing the intake of any of the lipid soluble
vitamins.
Excess accumulation of vitamin A in the liver can lead to toxicity which
manifests as bone pain, hepatosplenomegaly, nausea and diarrhea.
175
Vitamin D
Ergosterol
7-Dehydrocholesterol
Vitamin D2
Vitamin D3
Vitamin D is a steroid hormone that functions to regulate specific gene
expression following interaction with its intracellular receptor.
176
The biologically active form of the hormone is 1,25-dihydroxy vitamin
D3 (1,25-(OH)2D3, also termed calcitriol). Calcitriol functions primarily
to regulate calcium and phosphorous homeostasis.
Ergocalciferol (vitamin D2) is formed by uv irradiation of ergosterol. In
the skin 7-dehydrocholesterol is converted to cholecalciferol (vitamin
D3) following uv irradiation.
Vitamin D2 and D3 are processed to D2-calcitriol and D3-calcitriol,
respectively, by the same enzymatic pathways in the body.
The main symptom of vitamin D deficiency in children is rickets ‫داء‬
‫ كساح األطفال‬and in adults is osteomalacia ‫ لين العظام‬.
Rickets
is
characterized
improper
mineralization
development of the bones resulting in soft bones.
Vitamin E
Tocopherol
177
during
the
Vitamin E is a mixture of several related compounds known as
tocopherols.
Due to its Lipophilic nature, vitamin E accumulates in
cellular membranes, fat deposits and other circulating lipoproteins. The
major site of vitamin E storage is in adipose tissue.
The major function of vitamin E is to act as a natural antioxidant by
scavenging free radicals and molecular oxygen.
In particular vitamin E is important for preventing peroxidation of
polyunsaturated membrane fatty acids.
The vitamins E and C are interrelated in their antioxidant capabilities.
Active tocopherol can be regenerated by interaction with vitamin C
following scavenge of a peroxy free radical. Alternatively, tocopherol
can scavenge two peroxy free radicals and then be conjugated to
glucuronate for excretion in the bile.
The major symptom of vitamin E deficiency in humans is an increase in
red blood cell fragility ‫ قابلية التكسير‬.
Since vitamin E is absorbed from the intestines, any fat malabsorption
diseases can lead to deficiencies in vitamin E intake.
Vitamin K
The K vitamins exist naturally as K1 (phylloquinone) in green
vegetables and K2 (menaquinone) produced by intestinal bacteria and
K3 is synthetic menadione.
178
When administered, vitamin K3 is alkylated to one of the vitamin K2
forms of menaquinone.
Vitamin K1
Vitamin K2
Vitamin K3
The major function of the K vitamins is in the maintenance of normal
levels of the blood clotting proteins.
Fat malabsorptive diseases can result in vitamin K deficiency.
The primary symptom of a deficiency in infants is a hemorrhagic
syndrome.
179
Minerals
Minerals are inorganic micronutrients. They are categorized into 2
groups according to their amounts in our bodies. Major minerals include
calcium, chloride, magnesium, phosphorus, potassium; sodium and
sulphur, are found in our bodies in amounts greater than 5 grams.
However, trace minerals which are found in an amount less than 5
grams include chromium, copper, fluoride, iodine, iron, manganese,
selenium and zinc.
CALCIUM: Builds bones and teeth; aids in proper function of muscles,
heart, nerves, and iron utilization; helps blood coagulation; regulates
the passage of nutrients in and out of cells; relieves pain and cramps;
eases insomnia. NATURAL SOURCES: Dairy products, soybeans,
sunflower seeds, legumes, sardines.
MAGNESIUM: Reduces blood cholesterol; forms hard tooth enamel and
fights tooth decay; aids in converting blood sugar into energy; helps
regulate body temperature; aids nerve function and bone growth;
helps utilize Vitamins B, C, E; promotes absorption and metabolism of
other minerals; activates enzymes for metabolism of carbohydrates
and amino acids; prevents calcium deposits in the bladder, heart
180
attacks, depression, polio. NATURAL RESOURCES: Nuts, figs, seeds,
dark-green vegetables, wheat bran, avocados, bananas.
IRON: Present in all cells; one of the constituents of hemoglobin which
carries oxygen to the tissues by blood circulation. NATURAL
RESOURCES: Liver, meat, raw clams, oysters, oatmeal, nuts, beans,
wheat germ.
IODINE: Aids thyroid gland and prevents goiter; helps burn fat;
converts carotene into Vitamin A; aids absorption of carbohydrates
from small intestine; promotes growth; regulates energy production;
maintains hair, nails skin and teeth. NATURAL SOURCES: Kelp, seafood,
vegetables.
Vitamins and minerals
Vitamin or
Mineral
Examples of
Good Food
Sources
What It
Does
Recommended Daily Amount
(RDA) or Adequate
Upper Limit
(The Highest
Amount You Can
Take Without Risk
Calcium
Milk, yogurt,
Essential for bone
hard cheeses,
growth and
fortified cereals, strength, blood
spinach
clotting, muscle
contraction, and
the transmission
of nerve signals
Adults age 19-50: 1,000
milligrams/day
Adults age 51 and up: 1,200
milligrams/day
2,500
milligrams/day
Choline
(Vitamin B
complex)
Milk, liver, eggs, Plays a key role in
peanuts
the production of
cells and
neurotransmitters
Men: 550 milligrams/day
Women: 425 milligrams/day
Pregnantwomen: 450
milligrams/day
Breastfeedingwomen: 550
milligrams/day
3,500
milligrams/day
Chromium
Meats, poultry,
fish, some
cereals
Helps
controlblood
sugar levels
Adult men age 19-50: 35
micrograms/day
Adult men age 51 and up: 30
micrograms/day
Adult women age 19-50: 25
micrograms/day
Adult women age 51 and up:20
181
Unknown
micrograms/day
Pregnant women: 30
micrograms/day
Breastfeeding women: 45
micrograms/day
Copper
Seafood, nuts,
seeds, wheat
bran cereals,
whole grains
Fiber
Bran cereal,
peas, lentils,
black beans,
fruits,
vegetables
Fluoride
Important in
Adults: 900
themetabolism of micrograms/dayPregnant
iron
women: 1,000
micrograms/dayBreastfeeding
women: 1,300 micrograms/day
Helps with
digestion and the
maintenance of
blood sugar
levels; reduces
the risk
of heartdisease
Adult men age 19-50: 38
grams/dayAdult men age 51 and
up: 30 grams/dayAdult women age
19-50: 25 grams/dayAdult women
age 51 and up:21
grams/dayPregnant women: 28
grams/dayBreastfeeding
women: 29 grams/day
Fluoridated
Prevents the
Adult men: 4 milligrams/dayAdult
water, some sea
formation
women (including pregnant and
fish,
oftoothcavities an breastfeeding):3 milligrams/day
sometoothpaste d stimulates the
sand mouth
growth of bone
rinses
10,000
micrograms/day
None
10 milligrams/day
Folic Acid
(Folate)
Dark, leafy
vegetables;
enriched and
whole grain
breads; fortified
cereals
Key for the
development of
cells, protein
metabolism
andheart health;
in pregnant
women, helps
prevent birth
defects
Adults: 400
micrograms/dayPregnant
women: 600
micrograms/dayBreastfeeding
women: 500 micrograms/day
1,000
micrograms/day
Iodine
Processed foods
and iodized salt
Important in the
production
ofthyroid hormon
es
Adults: 150 micrograms/day
Pregnant women: 220
micrograms/day Breastfeeding
women: 290 micrograms/day
1,100
micrograms/day
Iron
Magnesium
Fortified cereals, Key component of
beans, lentils,
red blood cells
beef, eggs
and many
enzymes
Green leafy
vegetables,
Brazil nuts,
almonds,
soybeans,
halibut, quinoa
Helps with heart
rhythm, muscle
and nerve
function, bone
strength
Men: 8 milligrams/dayWomen age
19-50: 18 milligrams/dayWomen
age 51 and up: 8
milligrams/dayPregnant
women: 27 milligrams/day
Breastfeeding women: 9
milligrams/day
45 milligrams/day
Adult men age 19-30: 400
milligrams/dayAdult men age 31
and up: 420 milligrams/dayAdult
women age 19-30: 310
milligrams/day Adult women age
31 and up: 320
For magnesium in
food and water,
there is no upper
limit.
182
For magnesium
milligrams/dayPregnant
women: 350-360
milligrams/dayBreastfeeding
women: 310-320 milligrams/day
in supplementsor
fortified foods:
350
milligrams/day
Manganese
Nuts, beans and
other legumes,
tea, whole grains
Important in
forming bones
and some
enzymes
Men: 2.3 milligrams/day Adult
women: 1.8 milligrams/day
Pregnant women: 2.0
milligrams/day Breastfeeding
women: 2.6 milligrams/day
11 milligrams/day
Molybdenum
Legumes,
grains, nuts
Key in the
production of
some enzymes
Adults: 45
micrograms/dayPregnant and
breastfeeding women: 50
micrograms/day
2,000
micrograms/day
Phosphorus
Potassium
Milk and other
Allows cells to Adults: 700 milligrams/day
dairy products, function normally;
peas, meat,
helps the body
eggs, some
produce energy;
cereals and
key in bone
breads
growth
Sweet potato,
bananas, yogurt,
yellowfin tuna,
soybeans
Important in
Adults: 4,700 milligrams per
maintaining
dayBreastfeeding women: 5,100
normal fluid
milligrams/day
balance; helps
control blood
pressure; reduces
risk of kidney
stones
Selenium
Organ meats,
Protects cells
seafood, some
from damage;
plants (if grown regulates thyroid
in soil with
hormone
selenium) Brazil
nuts.
Adults: 55
micrograms/dayPregnant
women: 60
micrograms/dayBreastfeeding
women: 70 micrograms/day
Sodium
Foods to which Important for fluid
sodium chloride
balance
(salt) has been
added, like
salted meats,
nuts, butter, and
a vast number of
processed foods
Adults age 19-50: 1500
milligrams/dayAdults age 5170: 1,300 milligrams/dayAdults age
71 and up: 1,200 milligrams/day
Vitamin A
Sweet potato
Necessary for Men: 900
with peel,
normal vision, micrograms/dayWomen: 700
carrots, spinach, immune function, micrograms/day
fortified cereals
reproduction
183
Adults up to age
70: 4,000
milligrams/dayAd
ults over age
70: 3,000
milligrams/dayPre
gnant
women: 3500
milligrams/dayBre
astfeeding
women: 4,000
milligrams/day
Unknown
400
micrograms/day
2,300
milligrams/day
3,000
micrograms/day
Vitamin
B1(Thiamin)
Whole grain,
Allows the body
enriched,
to process
fortified
carbohydrates
products; bread; and some protein.
cereals
Men: 1.2
milligrams/dayWomen: 1.1
milligrams/dayPregnant and
breastfeeding women: 1.4
milligrams/day
Unknown
Vitamin
B2(Riboflavin)
Milk, bread
Key in metabolism
products,
and the
fortified cereals
conversion of
food into energy;
helps produce red
blood cells
Men: 1.3 milligrams/day Women:
1.1 milligrams/day Pregnant
Women: 1.4 milligrams/day
Breastfeeding Women: 1.6
milligrams/day
Unknown
Vitamin
B3(Niacin)
Vitamin
B5(Pantothenic
Acid)
Vitamin B6
Meat, fish,
Assists in
Men: 16 milligrams/dayWomen: 14
poultry, enriched digestion and the milligrams/dayPregnant
and whole grain
conversion of Women: 18 milligrams/day
breads, fortified food into energy; ?Breastfeeding women: 17
cereals
important in the milligrams/day
production of
cholesterol
Chicken, beef,
potatoes, oats,
cereals,
tomatoes
Important in fatty Adults: 5 milligrams/dayPregnant
acid metabolism women: 6
milligrams/dayBreastfeeding
women: 7 milligrams/day
Fortified cereals, Important for the
fortified soy
nervous system;
products, organ
helps the body
meats
metabolize
proteins and
sugar
Men age 19-50:1.3
milligrams/dayMen age 51 up: 1.7
milligrams/dayWomen age 1950: 1.3 milligrams/dayWomen age
51 up: 1.5 milligrams/dayPregnant
women: 1.9
milligrams/dayBreastfeeding
women: 2 milligrams/day
For niacin in
natural sources,
there is no upper
limit.
For niacin in
supplements or
fortified foods: 35
milligrams/day
Unknown
100
milligrams/day
Vitamin
B7(Biotin)
Liver, fruits,
meats
Helps with the Adults: 30
synthesis of fats, micrograms/dayBreastfeeding
glycogen and
women: 35 micrograms/day
amino acids
Unknown
Vitamin
B12(Cobalamin)
Fish, poultry,
meat, fortified
cereals
Important in the Adults: 2.4
production of red micrograms/dayPregnant
blood cells
women: 2.6
micrograms/dayBreastfeeding
women: 2.8 micrograms/day
Unknown
Vitamin C
Red and green
peppers, kiwis,
oranges,
strawberries,
broccoli
Antioxidant that
protects against
cell damage,
boosts the
immune system,
forms collagen in
the body
Men: 90 milligrams/dayWomen: 75
milligrams/dayPregnant
women: 85
milligrams/dayBreastfeeding
women: 120 milligrams/day
2,000
milligrams/day
Vitamin D
(Calciferol)
Fish liver oils,
fatty fish,
fortified milk
Crucial in
metabolizing
calcium for
Adults age 18-50: 5
micrograms/dayAdults age 5170: 10 micrograms/dayAdults over
50
micrograms/day
184
products,
fortified cereals;
also, formed
naturally as a
result of sunlight
exposure
Vitamin E
(alphatocopherol)
Vitamin K
Zinc
Fortified cereals,
sunflower seeds,
almonds, peanut
butter, vegetable
oils
healthy bones
age 70: 15
micrograms/dayPregnant and
breastfeeding women: 5
micrograms/day
Antioxidant that Adults (including pregnant
protects cells
women): 15
against damage milligrams/dayBreastfeeding
women: 19
Green
Important in blood Men: 120 micrograms/day
vegetables like clotting and bone
___
spinach,
health
Women (including pregnant and
collards, and
breastfeeding):90 micrograms/day
broccoli;
brussels
sprouts;
cabbage
Red meats,
some seafood,
fortified cereals
Supports the
body's immunity
and nerve
function;
important in
reproduction
Men: 11 milligrams/day
___
Women: 8 milligrams/dayPregnant
women: 11
milligrams/dayBreastfeeding
women: 12 milligrams/day
185
1,000
milligrams/day
Unknown
40 milligrams/day
6.HORMONE
A hormone is a chemical released by one or more cells that affects cells
in other parts of the organism. Only a small amount of hormone is
required to alter cell metabolism. Hormone is essentially a chemical
messenger that transports a signal from one cell to another.
Hormones in animals are often transported in the blood. Cells respond
to a hormone when they express a specific receptor for that hormone.
The hormone binds to the receptor protein, resulting in the activation
of a signal transduction mechanism that ultimately leads to cell typespecific responses.
Endocrine hormone molecules are secreted (released) directly into the
bloodstream.
Exocrine hormone (or ecto-hormones) are secreted directly into a duct,
and from the duct they either flow into the bloodstream or they flow
from cell to cell by diffusion in a process known as paracrine signalling.
Chemical classes of hormones
There are three different classes of hormone based on their chemical
composition:
1. Amines
Amines, such as nor-epinephrine, epinephrine, and dopamine, are
derived from single amino acids, in this case tyrosine.
186
Thyroid hormones such as 3,5,3’-tri-iodothyronine (T3) and 3,5,3’,5’tetra-iodothyronine (thyroxine, T4) make up a subset of this class
because they derive from the combination of two iodinated tyrosine
amino acid residues.
2. Peptide and protein
Peptide hormones and protein hormones consist of three (in the case
of thyrotropin-releasing hormone) to more than 200 (in the case of
follicle-stimulating hormone) amino acid residues and can have
molecular weights as large as 30,000.
All hormones secreted by the pituitary gland are peptide hormones, as
are:

Leptin from adipocytes

Ghrelin from the stomach

insulin from the pancreas
3. Steroid
Steroid
hormones
are
converted
cholesterol.
187
from
their
parent
compound,
Vitamin D3 (steroid hormone)
Mammalian steroid hormones can be grouped into five groups by the
receptors to which they bind:
1. Gluco corticoids
2. Mineralo corticoids
3. Androgens
4. Estrogens
5. Progestagens
Hormones as a signal
Hormonal signaling across this hierarchy (chain of commands) involves
the following:
1. Biosynthesis of a particular hormone in a particular tissue
2. Storage and secretion of the hormone
3. Transport of the hormone to the target cell(s)
4. Recognition of the hormone by an associated cell membrane or
intracellular receptor protein.
5. Relay (send) and amplification of the received hormonal signal
via a signal transduction process: This then leads to a cellular
response. The reaction of the target cells may then be recognized
188
by the original hormone-producing cells, leading to a downregulation in hormone production. This is an example of a
homeostatic negative feedback loop.
6. Degradation of the hormone.
As can be inferred from the hierarchical diagram, hormone biosynthetic
cells are typically of a specialized cell type, residing within a particular
endocrine gland, such as thyroid gland, ovaries, and testes.
Hormones exit their cell of origin via exocytosis or another means of
membrane transport. The hierarchical model is an over simplification of
the hormonal signaling process.
Cellular recipients of a particular hormonal signal may be one of
several cell types that reside within a number of different tissues, as is
the case for insulin, which triggers a diverse (varied) range of systemic
physiological affects.
Different tissue types may also respond differently to the same
hormonal signal. Because of this, hormonal signaling is elaborate
(complicated) and hard to dissect (divided).
Interactions with receptors
Most hormones initiate a cellular response by initially combining with
either a specific intracellular or cell membrane associated receptor
protein.
A cell may have several different receptors that recognize the same
hormone and activate different signal transduction pathways, or
189
alternatively different hormones and their receptors may invoke (refer
to) the same biochemical pathway.
For many hormones, including most protein hormones, the receptor is
membrane associated and embedded in the plasma membrane at the
surface of the cell.
The interaction of hormone and receptor typically triggers a cascade
(flow) of secondary effects within the cytoplasm of the cell, often
involving phosphorylation or de-phosphorylation of various other
cytoplasmic proteins, changes in ion channel permeability, or increased
concentrations of intracellular molecules that may act as secondary
messengers (e.g. cyclic AMP).
Some protein hormones also interact with intracellular receptors
located in the cytoplasm or nucleus by an intracrine mechanism.
For hormones such as steroid or thyroid hormones, their receptors are
located intracellularly within the cytoplasm of their target cell.
In order to bind their receptors these hormones must:

Cross the cell membrane.

Combined with receptor.

The combined hormone-receptor complex moves across the
nuclear membrane into the nucleus of the cell.

Hormone binds to specific DNA sequences.

Hormone is effectively amplifying or suppressing the action of
certain genes.

Hormones affecting protein synthesis.
190
However, it has been shown that not all steroid receptors are located
intracellularly, some are plasma membrane associated.
An important consideration, dictating the level at which cellular signal
transduction pathways are activated in response to a hormonal signal
is the effective concentration of hormone-receptor complexes that are
formed.
ENDOCRINE DISEASES
A disease due to a disorder of the endocrine system is often called a
"HORMONE
IMBALANCE",
but
is
technically
known
as
an
ENDOCRINOPATHY or ENDOCRINOSIS.
Endocrine disease
Classification and external resources
Major endocrine glands. (Male left, female on the right.)
1. Pineal gland
2. Pituitary gland
Thymus
5. Adrenal gland
Ovary
8. Testes
191
3. Thyroid gland
6. Pancreas
4.
7.
7.METABOLISM
METABOLISM is the set of chemical reactions that occur in
living organisms in order to maintain life. These processes
allow organisms to grow and reproduce, maintain their
structures, and respond to their environments.
Metabolism
is
usually
divided
into
two
categories.
CATABOLISM breaks down large molecules, for example to
harvest energy in cellular respiration. ANABOLISM , on the
other hand, uses energy to construct components of cells
such as proteins and nucleic acids.
The chemical reactions of metabolism are organized into
metabolic pathways, in which one chemical is transformed
into another by a sequence of enzymes.
Most of the structures that make up animals, plants and
microbes are made from three basic classes of molecule:
1. amino acids
2. carbohydrates
3. lipids
As these molecules are vital for life, metabolism focuses on
making these molecules, in the construction of cells and
tissues, or breaking them down and using them as a source
of energy, in the digestion and use of food.
192
Many important biochemicals can be joined together to make
polymers such as DNA and proteins. These macromolecules
are essential parts of all living organisms.
CATABOLISM
Catabolism is the set of metabolic processes that break down
large molecules. These include breaking down and oxidizing
food molecules. The purpose of the catabolic reactions is to
provide the energy and components needed by anabolic
reactions. The exact nature of these catabolic reactions differ
from organism to organism.
The most common set of catabolic reactions in animals can
be separated into three main stages:
1. Large organic molecules (proteins, carbohydrates or
lipids) are digested into their smaller components
outside cells.
2. These smaller molecules are taken up by cells and
converted
to
smaller
molecules,
usually
acetyl
coenzyme A, which releases some energy.
3. The acetyl group of CoA is oxidized to H2O and CO2 in
the citric acid cycle and electron transport chain,
releasing the energy that is stored by reducing the
coenzyme NAD+ (nicotinamide adenine dinucleotide)
into NADH.
193
Digestion
Macromolecules such as starch, cellulose or proteins cannot
be rapidly taken up by cells and need to be broken into their
smaller units before they can be used in cell metabolism.
Several common classes of enzymes digest these polymers.
These digestive enzymes include proteases that digest
proteins into amino acids, as well as glycoside hydrolazes
that digest polysaccharides into monosaccharides. Lipases
digest lipids into fatty acids and glycerol.
Animals secrete these enzymes from specialized cells in
their guts. The amino acids or sugars released by these
extracellular enzymes are then pumped into cells by specific
active transport proteins.
Energy from organic compounds
Carbohydrate catabolism is the breakdown of carbohydrates
into smaller units. Carbohydrates are usually taken into cells
once they have been digested into monosaccharides.
Once inside, the major route of breakdown is glycolysis,
where sugars such as glucose and fructose are converted
into pyruvate and some ATP is generated.
194
Pyruvate is an intermediate in several metabolic pathways,
but the majority is converted to acetyl-CoA and fed into the
citric acid cycle.
Although some more ATP is generated in
the citric acid cycle, the most important product is NADH,
which is made from NAD+ as the acetyl-CoA is oxidized.
An alternative route for glucose breakdown is the pentose
phosphate pathway, which reduces the coenzyme NADPH
and produces pentose sugars such as ribose, the sugar
component of nucleic acids.
Fats are catabolized by hydrolysis to free fatty acids and
glycerol. The glycerol enters glycolysis and the fatty acids
are broken down by beta oxidation to release acetyl-CoA,
which then is fed into the citric acid cycle.
Fatty acids release more energy upon oxidation than
carbohydrates because carbohydrates contain more oxygen
in their structures.
Amino acids are either used to synthesize proteins and other
biomolecules, or oxidized to urea and carbon dioxide as a
source of energy. The oxidation pathway starts with the
removal of the amino group by a transaminase. The amino
group is fed into the urea cycle, leaving a deaminated carbon
skeleton in the form of a keto acid. Several of these keto
acids are intermediates in the citric acid cycle, for example
195
the deamination of glutamate forms α-ketoglutarate. The
glucogenic amino acids can also be converted into glucose,
through gluconeogenesis.
ANABOLISM
Anabolism is the set of constructive metabolic processes
where the energy released by catabolism is used to
synthesize complex molecules. In general, the complex
molecules that make up cellular structures are constructed
step-by-step from small and simple precursors.
Anabolism involves three basic stages:
1. The production of precursors such as amino acids,
monosaccharides, isoprenoids and nucleotides.
2. Their activation into reactive forms using energy from
ATP.
3. The
assembly
of
these
precursors
into
complex
molecules such as proteins, polysaccharides, lipids and
nucleic acids.
196
Carbohydrates Metabolism
In carbohydrate anabolism, simple organic acids can be
converted into monosaccharides such as glucose and then
used to assemble polysaccharides such as starch. The
generation of glucose from compounds like pyruvate, lactate,
glycerol, glycerate 3-phosphate and amino acids is called
gluconeogenesis.
Gluconeogenesis converts pyruvate to glucose-6-phosphate
through a series of intermediates, many of which are shared
with glycolysis.
However, this pathway is not simply
glycolysis run in reverse, as several steps are catalyzed by
non-glycolytic enzymes.
Polysaccharides and glycans are made by the sequential
addition of monosaccharides by glycosyltransferase from a
reactive sugar-phosphate donor such as uridine diphosphate
glucose (UDP-glucose) to an acceptor hydroxyl group on the
growing polysaccharide.
197
Glycolysis
Digestion of Dietary Carbohydrates
Dietary carbohydrate from which humans gain energy enter
the body in complex forms, such as disaccharides and the
polymers starch (amylose and amylopectin) and glycogen.
The polymer cellulose is also consumed but not digested. The
first step in the metabolism of digestible carbohydrate is the
conversion of the higher polymers to simpler, soluble forms
that can be transported across the intestinal wall and
delivered to the tissues.
Oxidation of glucose is known as glycolysis. Glucose is
oxidized to either lactate or pyruvate. Under aerobic
conditions, the dominant product in most tissues is pyruvate
and the pathway is known as aerobic glycolysis. When
oxygen is depleted, as for instance during prolonged
vigorous exercise, the dominant glycolytic product in many
tissues is lactate and the process is known as anaerobic
glycolysis.
The Energy Derived from Glucose Oxidation
198
Glucose
+
2 ADP + 2 NAD+ + 2 Pi
2 Pyruvate + 2 ATP + 2 NADH + 2 H+
The NADH generated during glycolysis is used to fuel
mitochondrial ATP synthesis via oxidative phosphorylation,
producing either two or three equivalents of ATP.
The net yield from the oxidation of 1 mole of glucose to 2
moles of pyruvate is, therefore, either 6 or 8 moles of ATP.
Complete oxidation of the 2 moles of pyruvate, through the
Citric Acid Cycle (TCA cycle) yields an additional 30 moles of
ATP; the total yield, therefore being either 36 or 38 moles of
ATP from the complete oxidation of 1 mole of glucose to CO2
and H2O.
The citric acid cycle is part of a metabolic pathway involved
in the chemical conversion of carbohydrates, fats and
proteins into carbon dioxide and water to generate a form of
usable energy.
199
The Individual Reactions of Glycolysis
The pathway of glycolysis can be seen as consisting of 2
separate phases.
 The first is the chemical priming phase requiring energy
in the form of ATP.
 The second is considered the energy-yielding phase.
In the first phase,
2 equivalents of ATP are used to convert glucose to fructose
1,6-bisphosphate (F1,6BP).
In the second phase,
fructose 1,6-bisphosphate (F1,6BP) is degraded to pyruvate,
with the production of 4 equivalents of ATP and 2
equivalents of NADH.
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201
Pathway of Glycolysis from glucose to pyruvate (Lactate).
Embden-Mayerhof- ‫دورة امدن مايرهوف‬
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Anaerobic Glycolysis
Under aerobic conditions, pyruvate in most cells is further
metabolized via the TCA cycle. Under anaerobic conditions
and in erythrocytes under aerobic conditions, pyruvate is
converted to lactate by the enzyme lactate dehydrogenase
(LDH), and the lactate is transported out of the cell into the
circulation.
The conversion of pyruvate to lactate, under anaerobic
conditions, provides the cell with a mechanism for the
oxidation of NADH (produced during the G3PDH reaction) to
NAD+; which occurs during the LDH catalyzed reaction.
Aerobic glycolysis generates substantially more ATP per mole
of glucose oxidized than does anaerobic glycolysis.
The utility of anaerobic glycolysis, to a muscle cell when it
needs large amounts of energy, stems from the fact that the
rate of ATP production from glycolysis is approximately 100X
faster than from oxidative phosphorylation.
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Gluconeogenesis
Gluconeogenesis is the biosynthesis of new glucose, (i.e. not
glucose from glycogen).
The production of glucose from other metabolites is
necessary for use as a fuel source by the brain, testes,
erythrocytes and kidney medulla since glucose is the sole
energy source for these organs.
During starvation, however, the brain can derive energy from
ketone bodies which are converted to acetyl-CoA.
204
205
206
Substrates for Gluconeogenesis
Lactate:
Lactate is a predominate source of carbon atoms for glucose
synthesis by gluconeogenesis. During anaerobic glycolysis in
skeletal muscle, pyruvate is reduced to lactate by lactate
dehydrogenase (LDH).
LDH
Pyruvate
Lactate
This reaction serves two critical functions during anaerobic
glycolysis:
1. LDH reaction requires NADH and yields NAD+ which is
then
available
for
use
by
the
glyceraldehyde-3-
phosphate dehydrogenase reaction of glycolysis.
2. The lactate produced by the LDH reaction is released to
the blood stream and transported to the liver where it is
converted to glucose. The glucose is then returned to
the blood for use by muscle as an energy source and to
replenish glycogen stores. This cycle is termed the
Cori cycle.
207
Pyruvate:
Pyruvate, generated in muscle and other peripheral tissues,
can be transaminated to alanine which is returned to the
liver for gluconeogenesis.
The transamination reaction requires an α-amino acid as
donor of the amino group, generating an α-keto acid in the
process. This pathway is termed the
cycle.
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glucose-alanine
The
glucose-alanine
mechanism
for
cycle
muscle
is,
to
therefore,
eliminate
an
nitrogen
indirect
while
replenishing ‫ يزززود‬its energy supply. However, the major
function of the glucose-alanine cycle is to allow non-hepatic
tissues to deliver the amino portion of catabolized amino
acids to the liver for excretion as urea. Within the liver the
alanine is converted back to pyruvate and used as a
gluconeogenic substrate (if that is the hepatic requirement)
or oxidized in the TCA cycle. The amino nitrogen is converted
to urea in the urea cycle and excreted by the kidneys.
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Citric Acid Cycle
The citric acid cycle — also known as the tricarboxylic acid
cycle (TCA cycle), the Krebs cycle, is a series of enzymecatalysed chemical reactions of central importance in all
living cells that use oxygen as part of cellular respiration. In
eukaryotes, the citric acid cycle occurs in the matrix of the
mitochondrion. In aerobic organisms, the citric acid cycle is
part of a metabolic pathway involved in the chemical
conversion of carbohydrates, fats and proteins into carbon
dioxide and water to generate a form of usable energy. Other
relevant reactions in the pathway include those in glycolysis
and pyruvate oxidation before the citric acid cycle, and
oxidative phosphorylation after it. In addition, it provides
precursors for many compounds including some amino acids
and
is
therefore
functional
even
in
cells
performing
fermentation.
The TCA cycle showing enzymes, substrates and products.
The
GTP
generated
during
the
succinate
thiokinase
(succinyl-CoA synthetase) reaction is equivalent to a mole of
ATP by virtue of the presence of nucleoside diphosphokinase.
The 3 moles of NADH and 1 mole of FADH2 generated during
each
round
of
the
cycle
feed
into
the
oxidative
phosphorylation pathway. Each mole of NADH leads to 3
moles of ATP and each mole of FADH2 leads to 2 moles of
210
ATP. Therefore, for each mole of pyruvate which enters the
TCA cycle, 12 moles of ATP can be generated. IDH =
isocitrate
dehydrogenase.
α-KGDH
=
α-ketoglutarate
dehydrogenase. MDH = malate dehydrogenase. Place mouse
over cycle intermediate names to see their structures.
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CITRIC ACID CYCLE (TCA CYCLE)
Krebs ‫دورة‬
212