Lecture № 15
Di- and
polysaccharides.
Terpenes.
Ass. Medvid I.I.
Ass. Burmas N.I
Outline
1. Oligosaccharides.
2. The following functions of carbohydrates in humans.
3.Classification of disaccharides:
a) maltose;
b) cellobiose;
c) lactose;
d) saccharose.
4. Polysaccharides (glucanes).
a) Homopolysaccharides:
- Structure, composition and properties of cellulose.
- Structure, composition and properties of starch.
- Glycogen, dextranes, inuline, pectin compounds, chitin.
b) Heteropolysaccharides.
5. Glycoconjugates.
6. Lipids.
7. Chemical properties of fats
8. Phospholipids. Waxes.
9. Nonsaponifiable lipids.
10. Terpenes and terpenoids. Terpene biosynthesis.
11. Classification of terpenes.
12. Carotenoids.
13. Steroids.
14. Properties of cholesterol. Biosynthesis of cholesterol.
15. Vitamins.
16. Water-soluble vitamins.
17.Water insoluble (lipid-soluble) vitamins.
1. Oligosaccharides.
• The term “oligosaccharide” is often used for carbohydrates that
•
•
consist of between two and ten monosaccharide units.
Oligosaccharides are carbohydrates that contain from two
to ten monosaccharide units.
Disaccharides are the most common type of oligosaccharide.
Disaccharides are carbohydrates composed of two
monosaccharide units covalently bonded to each other. Like
monosaccharides, disaccharides are crystalline, water-soluble
substances. Saccharose (table sugar) and lactose (milk sugar)
are disaccharides. Within the human body, oligosaccharides are
often found associated with proteins and lipids in complexes
that have both structural and regulatory functions. Free
oligosaccharides, other than disaccharides, are seldom
encountered in biological systems
Complete hydrolysis of an oligosaccharide produces
monosaccharides. Upon hydrolysis, а disaccharide produces
two monosaccharides, а trisaccharide three monosaccharides, а
hexasaccharide six monosaccharides, and so on.
• Carbohydrates are the most abundant class of bioorganic
molecules on planet Earth. Although their abundance in the
human body is relatively low, carbohydrates constitute about
75% by mass of dry plant materials.
• Green (chlorophyll-containing) plants produce carbohydrates
via photosynthesis. In this process, carbon dioxide from the air
and water from the soil are the reactants, and sunlight absorbed
by chlorophyll is the energy source.
• Plants have two main uses for the carbohydrates they produce.
In the form of cellulose, carbohydrates serve as structural
elements, and in the form of starch, they provide energy
reserves for the plants.
• Dietary intake of plant materials is the major carbohydrate
source for humans and animals. The average human diet
should ideally be about two-thirds carbohydrate by mass.
2. The following functions of carbohydrates in
humans.
Carbohydrates have the following functions in
humans:
1. Carbohydrate oxidation provides energy
2. Carbohydrate storage, in the form of glycogen,
provides а short- term energy reserve.
3. Carbohydrates supply carbon atoms for the synthesis
of other biochemical substances (proteins, lipids, and
nucleic acids).
4. Carbohydrates form part of the structural framework
of DNA and RNA molecules.
5. Carbohydrate "markers" on cell surfaces play key
roles in cell -cell recognition processes.
3.Classification of disaccharides
(1) Nоn-reducing disaccharides. In these disaccharides the
two hexose units are linked together through their
reducing (i е. aldehydic or ketonic) groups which is
,
in aldoses and
, in ketoses. Now in such cases since
the reducing groups of both hexoses are lost, the resulting
compound (disaccharide) will be non-reducing. Hence
such disaccharides do not form osazone do not show
mutarotation and do not react with reagents like Feling’s
solution, Tollen’s reagent, etc. Important example of nonreducing disaccharides is saccharose.
(2) Reducing disaccharides. In these disaccharides,
one hexose unit is linked through its reducing carbon to
the non-reducing carbon (C4 or С6) of the other Now
since the reducing group of one of the hexoses is not
involved, the resulting disaccharide will be а reducing
sugar. Maltose and lactose are examples of reducing
disaccharides.
• As mentioned earlier, disaccharides are those sugars which on
•
hydrolysis give two moles of monosaccharides general these
are sweet-testing crystalline, water-soluble substances, easily
hydrolysed by enzymes and dilute mineral acids. The common
disaccharides have the general formula C12H22O11 which
during hydrolysis take one molecule of water to form two
hexoses.
Disaccharides are formed by intermolecular dehydration
between two monosaccharide molecules, e.g. In the formation
of disaccharides, at least one monosaccharide unit is linked to
the other through the glycosidic carbon atom. In other words
we can say that in the formation of disaccharide, reducing
property of at least one hexose unit is lost. Hence
disaccharides may be considered as glycosides in which both
components of the molecules are sugars. Disaccharides may
exist in two types, namely non-reducing and reducing
depending on the fact that С1 of one hexose is linked to the
carbonyl carbon at other carbon atom of other hexose. Weak
oxidizing agents, such as Tollens, Feling's, and Benedict's
solutions, oxidize the carbonyl group end of а monosaccharide
to give an -onic acid.
Disaccharides. А monosaccharide that has cyclic forms
(hemiacetal or hemiketal) can react with an alcoho1 to form а
glycoside (acetal or ketal). This same type of reaction can be used
to produce а disaccharide, а carbohydrate in which two
monosaccharides are bonded together. In disaccharide formation,
one of the monosaccharide reactants functions as а hemiacetal or
hemiketal, and the other functions as an alcohol.
Monosaccharide + monosaccharide = disaccharide + Н2O
The bond that links the two monosaccharides of а disaccharide together is called а glycosidic
linkage. А glycosidic linkage is the carbon-oxygen-carbon bond that joins the two components of
а glycoside together. The bond that links the two monosaccharides of а disaccharide together is
called а glycosidic linkage. We now examine the structures and properties of four important
disaccharides: maltose, cellobiose, lactose, and saccharose. As we consider details of the
structures of these compounds, we will find that the configuration (α or β) at carbon-1 of the
reacting monosaccharides is often of prime importance.
Maltose, often called malt sugar, is produced by breaking
down the polysaccharide starch, as takes place in plants when
seeds germinate and in human beings during starch digestion.
It is а common ingredient in baby foods and is found in malted
milk. Malt (germinated barley that has been baked and ground)
contains maltose; hence the name malt sugar. Structurally,
maltose is made up of two D-glucopyranose units, one of
which must be -D-glucose. The formation of maltose from
two glucose molecules is as follows:
-D-Glucose
-D-Glucose
-(1-4)-linkage
So, α-maltose can be named as 4-O-(α-Dglucopyranosido)-α-D-glucopyranose, β-maltose – 4O-(α-D-glucopyranosido)-β-D-glucopyranose.
The glycosidic linkage between the two glucose units is called
an (1 - 4) linkage. The two ОН-groups that form the linkage
are attached, respectively, to carbon-1 of the first glucose unit
(in an a configuration) and to carbon-4 of the second. Maltose
is а reducing sugar, because the glucose unit on the right has а
hemiacetal carbon atom (С-1).Thus this glucose unit can open
and close; it is in equilibrium with its open-chain aldehyde
form. This means there are actually three forms of the maltose
molecule: -maltose, -maltose, and the open-chain form. In
the solid state, the -form is dominant. The most important
chemical reaction of maltose is hydrolysis. Hydrolysis of Dmaltose, whether in а laboratory flask or in а living organism,
produces two molecules of D-glucose.
CH
2
O
H
CH
OH
OH
H
H
O
H
OH
OH
H
[O]
2
CH
OH
O
H
OH
OH
H
2
OH
OH
H
H
H
H
O
O
H
OH
H
HO
HO
H
CH
OH
O
H
H
2
OH
C
OH
H
OH
maltoboinic acid
H
OH
CH 2 OH
CH 2 OH
H
HO
O
H
H
OH
H
O
O
CH3OH (HCl,gas)
H
H
OH
OH H
HO
H
OH
H
CH 2 OH
CH 2 OH
OH
O
H
H
OH
H
H
O
OH
O
H
OH H
H
OCH 3
OH
methylmaltozide
CH2OCH3
O
OH
H
H H
H
OCH3
H
H
O OCH3
OCH3
CH3O
OCH3
H OCH3
H
CH2OCH3
CH3J або (CH3)2SO4
CH2OH
O
OH
H
H H
H
OH H O OH H
HO
CH2OH
H
OH
H
OH
(CH3CO)2O
(Ac = CH3CO)
HOH, H+
OH
CH2OAc
O
OH
H
H H
H
OAc H O OAc H
AcO
OAc
H OAc
H
CH2OAc
OAc
HOH, H+
CH2OCH3
O
H H
CH2OCH3
HOH, H+
H
CH3O
H
OCH H
3
H
HOH, H+
O H
O
OCH3
OH
OCH3
H
CH2OAc
+
CH3OH
OCH3
CH2OAc
O
O H
H
H H
H
OAc H
OAc H
O
AcO
OAc
OAc
H
H
OH
+
CH3COOH
Cellobiose is produced as an intermediate in the
hydrolysis of the polysaccharide cellulose. Like maltose,
cellobiose contains two D-glucose monosaccharide units. It
differs from maltose in one of D-glucose units - the one
functioning as а hemiacetal - must have а -configuration
instead of the а configuration of maltose. This change in
configuration gives а (1-4) glycosidic linkage.
-D-Glucose
(1-4)-linkage
α-cellobiose can be named as 4-O-(β-Dglucopyranosido)-α-D-glucopyranose, β-cellobiose – 4O-(β-D-glucopyranosido)-β-D-glucopyranose.
Like maltose, cellobiose is a reducing sugar, has three
isomeric forms in aqueous solution, and upon hydrolysis
produces two D-glucose molecules. Despite these similarities,
maltose and cellobiose have different biological behaviors.
These differences are related to the stereochemistry of their
glycosidic linkages. Maltase, the enzyme that breaks the
glucose-glucose (1-4) linkage present in maltose, is found
both in the human body and in yeast. Consequently, maltose is
digested easily by humans and is readily fermented by yeast.
Both the human body and yeast lack the enzyme cellobiase
needed to break the glucose - glucose (1-4) linkage of
cellobiose. Thus cellobiose cannot be digested by humans or
fermented by yeast. In maltose and cellobiose, the two units of
the disaccharide are identical - two glucose units in each case.
Maltose and cellobiose have different arrangement in space. In
maltose molecule α-glycosidic linkage has axial arrangement,
in cellobiose molecule β-glycosidic linkage – equatorial. Its
cases club-similar structure of amylose and linear structure of
cellulose.
Lactose includes -D-galactopyranose unit and а Dglucopyranose unit joined by -(1-4) glycosidic linkage
-D-galactose
-D-Glucose
(1-4)-linkage
The glucose hemiacetal center is active when galactose bonds to glucose in the
formation of lactose, so lactose is а reducing sugar (the glucose ring can open to give
an aldehyde).Lactose is the major sugar found in milk. This accounts for its common
name, milk sugar. Enzymes in animal mammary glands take glucose from the
bloodstream and synthesize lactose in а four-step process. Epimerization of glucose
yields galactose, and then the (1-4) linkage forms between а galactose and а glucose
unit. Lactose is an important ingredient in commercially produced infant formulas that
are designed to simulate mother' s milk. Souring of milk is caused by the conversion of
lactose to lactic acid by bacteria in the milk. Pasteurization of milk is а quick-heating
process that kills most of the bacteria and retards the souring process. Lactose can be
hydrolyzed by acid or by the enzyme lactase, forming an equimolar mixture of
galactose and glucose. In the human body, the galactose produced in such way is then
converted to glucose by other enzymes. The genetic condition lactose intolerance, an
inability of the human digestive system to hydrolyze lactose.
α-lactose can be named as 4-O-(β-D-galactopyranosido)-α-D-glucopyranose,
β-lactose – 4-O-(β-D-galactopyranosido)-β-D-glucopyranose.
Arrangement in space is similar to cellobiose:
Saccharose, common table sugar, is the most
abundant of all disaccharides and occurs throughout
the plant kingdom. It is produced commercially from
the juice of sugar cane and sugar beets. Sugar cane
contains up to 20 % by mass saccharose, and sugar
beets contain up to 17 % by mass saccharose. The
two monosaccharide units present in -D-saccharose
molecule are -D-glucose in form of -Dglucopyranose and -D-fructose in form of -Dfructofuranose. The glycosidic linkage is not а (1-4)
linkage, as was in case with maltose, cellobiose, and
lactose. It is instead an ,(1 - 2) glycosidic linkage.
The ОН-group on carbon-2 of D-fructose (the
hemiketal carbon) reacts with the ОН-group on
carbon-l of D-glucose (the hemiacetal carbon).
Saccharose can be named as 2-O-(α-D-glucopyranosido)-β-Dfructofuranose.
Saccharose, unlike maltose, cellobiose, and lactose,
is а non-reducing sugar. No helmiacetal or hemiketal
center is present in the molecule, because the glycosidic
linkage involves the reducing ends of both
monosaccharides. Saccharose, in the solid state and in
solution, exists in only one form - there are no  and 
isomers, and an open-chain form is not possible.
Saccharase, the enzyme needed to break the ,(1 - 2)
linkage in saccharose, is present in the human body.
Hence saccharose is an easily digested substance.
• Saccharose hydrolysis (digestion) produces an equimolar
•
mixture of glucose and fructose called invert sugar. When
saccharose is cooked with acid-containing foods such as fruits
or berries, partial hydrolysis takes place, forming some invert
sugar. Jams and jellies prepared in this manner are actually
sweeter than the pure saccharose added to the original mixture,
because one-to-one mixtures of glucose and fructose taste
sweeter than saccharose.
Saccharose is dextrorotatory. On hydrolysis it gives one
molecule of glucose and one molecule of fructose. Now since
fructose is more strongly laevorotatory than the dextrorotatory
property of glucose, the mixture (product) after hydrolysis will
be laevorotatory. This reaction is also as inversion of sugar
because the dextrorotatory case sugar is converted into
laevorotatory product due to hydrolysis. The mixture of
glucose and fructose is called invert sugar.
dextrorotatory
laevorotatory
4. Polysaccharides (glucanes)
А polysaccharides (glucanes) contains many
monosaccharide units bonded to each other by glycosidic
linkages. The number of monosaccharide units in
polysaccharides varies from а few hundred to hundreds
of thousands. Polysaccharides are polymers. In some,
the monosaccharides are bonded together in а linear
(unbranched) chain. In others, there is extensive
branching of the chains. Unlike monosaccharides and
most disaccharides, polysaccharides are not sweet and
do not give positive reaction with Tollens, Benedict’s,
and Feling’s solutions. They have limited water solubility
because of their size. However, the ОН-groups present
in molecule can individually become hydrated by water
molecules. The result is usually а thick colloidal
suspension of the polysaccharide in water.
Polysaccharides, such as flour and cornstarch, are often
used as thickening agents in sauces, desserts, and
gravy.
Linear and branched structure of
polysaccharides
Although there are many naturally occurring
polysaccharides, in this section we will focus on only four of
them: cellulose, starch, glycogen, and chitin. All play vital
roles in living systems - cellulose and starch in plants,
glycogen in humans and other animals, and chitin in
arthropods.
Polysaccharides may be divided into two classes:
homopolysaccharides, which are composed of one type of
monosaccharide units, and heteropolysaccharides, which
contain two or more different types of monosaccharide units.
Starch, glycogen and cellulose are homoglycans as they
are made of only glucose and are called glucanes or
glucosanes. Homopolysaccharides which containe only
pentoses called pentosanes, hexoses – hexosanes. On the other
hand, mucopolysaccharides like hyaluronic acid and
chondroitine sulphate are heteroglycanes as they are made up
of different monosaccharide units.
Common formula for pentosanes – (C5H8O4)n, for hexosanes
– (C6H10O5)n.
Homopolysaccharides
Structure, composition and properties of
cellulose.
Cellulose is the most abundant polysaccharide. It
is the structural component of the cell walls of plants.
Approximately half of all the carbon atoms in the
plant kingdom are contained in cellulose molecules.
Structurally, cellulose is а linear (unbranched) Dglucose polymer in which the glucose units are linked
by (1-4) glycosidic bonds.
• At heating with mineral acids cellulose
hydrolyzed by the following scheme:
In cellulose glucopyranose remainders
have linear structure and hydrogen bonds:
Typically, cellulose chains contain about 5000 glucose units,
which gives macromolecules with molecular masses of about
900,000. Cotton is almost pure cellulose (95 %) and wood is about
50 % cellulose. Even though it is а glucose polymer, cellulose is
not а source of nutrition for human beings. Humans lack the
enzymes capable of catalyzing the hydrolysis of  (1- 4) linkages
in cellulose. Even grazing animals have the enzymes necessary for
cellulose digestion. However, the intestinal tracts of animals such
as horses, cows, and sheep contain bacteria that produce cellulose,
an enzyme that can hydrolyze  (1- 4) linkages and produce free
glucose from cellulose. Thus grasses and other plant materials are а
source of nutrition for grazing animals. The intestinal tracts of
termites contain the same microorganisms, which enable termites
to use wood as their source of food. Microorganisms in the soil can
also metabolize cellulose, which makes possible the biodegradation
of dead plants. Despite its nondigestibility, cellulose is still an
important component of а balanced diet. It serves as dietary fiber.
Dietary fiber provides the digestive tract with "bulk" that helps
move food through the intestinal tract and facilitates the excretion
of solid wastes. Cellulose readily absorbs water, leading to softer
stools and frequent bowel action. Links have been found between
the length of time stools spend in the colon and possible colon
cancer.
High-fiber food may also play а role in weight control.
Obesity is not seen in parts of the world where people eat large
amounts of fiber-rich foods. Many of the weight-loss products
on the market are composed of bulk-inducing fibers such as
methylcellulose.
•
FIGURE. Cellulose microfibrils.
Some fibers bind lipids such as cholesterol and
carry out them of the body with the feces. This
lowers blood lipid concentrations and possibly the
risk of heart and artery disease.
Structure, composition and properties of starch.
Starch, like cellulose, is а polysaccharide containing
only glucose units. It is the storage polysaccharide in
plants. If excess of glucose enters а plant cell, it is
converted to starch and stored for later use. When the
cell cannot get enough glucose from outside, it
hydrolyzes starch to release glucose. Iodine is often
used to test the presence of starch in solution. Starchcontaining solutions turn а dark blue when iodine is
added. As starch is broken down through acid or
enzymatic hydrolysis to glucose monomers, the blue
color disappears. Two different polyglucose
polysaccharides can be isolated from most starches:
amylose and amylopectin. Amylose, а straight-chain
glucose polymer, usually accounts for 15% — 20% of
the starch; amylopectin, а highly branched glucose
polymer, accounts for the remaining 80% — 85% of the
starch.
In amylose's structure, the glucose units are connected by
(1- 4) glycosidic linkages.
Starch (amylose)
The number of glucose units present in an amylose chain
depends on the source of the starch; 200 – 350 monomer units
are usually present. Amylopectin, the other polysaccharide in
starch, is similar to amylose, but has а high degree branched
structure in the polymer. А one branch link containe 20-25
glucose units. The number of glucose units present in an
amylopectin chain consists of 1000 and more units. The branch
points involve (1 – 6) linkages:
Starch (amylopectin)
Because of the branching, amylopectin has а
larger average molecular mass than the linear
amylose. The average molecular mass of amylose is
40000 or more; it is 1-6 mln. for amylopectin. Note
that all of the glycosidic linkages in starch (both
amylose and amylopectin) are of the -type. In
amylose, they are all (1 - 4); in amylopectin, both
(1 -4) and (1 -6) linkages are present. Because а
linkages can be broken through hydrolysis within the
human digestive tract (with the help of the enzyme
amylase), starch has nutritional value for humans.
The starches present in potatoes and cereal grains
(wheat, rice, corn, etc.) account for approximately
two-thirds of the world' s food consumption.
Fermentayion hydrolysis of starch is shown below:
Glycogen, chitin.
Glycogen, like cellulose and starch, is а polysaccharide
containing only glucose units. It is the glucose storage
polysaccharide in humans and animals. Its function is thus similar
to that of starch in plants, and it is sometimes referred to as animal
starch. Liver cells and muscle cells are the storage sites for
glycogen in humans. Glycogen has а structure similar to that of
amylopectin; all glycosidic linkages are of the -type, and both
(1-4) and (1-6) linkages are present. Glycogen and amylopectin
differ in the number of glucose units between branches and the
total number of glucose units present in а molecule. Glycogen is
about three times more highly branched than amylopectin, and it is
much larger, with а molar mass. А one branch link containe 8-12
glucose units, rare – 2- 4. When excess of glucose is present in the
blood (normally from eating too much starch), the liver and muscle
tissue convert the excess of glucose to glycogen, which is then
stored in these tissues. Whenever the glucose blood level drops
(from exercise, fasting, or normal activities), some stored glycogen
is hydrolyzed back to glucose. These two opposing processes are
called glycogenesis and glycogenolysis, the formation and
decomposition of glycogen, respectively.
•
•
•
Glycogen is an ideal storage form for glucose. The large
size of these macromolecules prevents them from diffusing out
of cells. Also, conversion of glucose to glycogen reduces
osmotic pressure. Cells would burst because of increased
osmotic pressure if all of the glucose in glycogen were present
in cells in free form. High concentrations of glycogen in а cell
sometimes cases precipitate or crystallize into glycogen
granules. These granules are discernible in photographs of
cells under electron microscope magnification. The glucose
polymers amylose, amylopectin, and glycogen compare as
follows in molecular size and degree of branching:
Amylose: Up to 1000 glucose units; no branching
Amylopectin: Up to 100,000 glucose units; branch points
every 20-25 glucose units
Glycogen: Up to 1,000,000 glucose units; branch points every
8-12 glucose units
FIGURE. Structure of amylopectine (а), glycogen (b)
Dextranes
• Dextranes have bacterial origin, contain remainders of α-D-
glucopyranose. Dextranes obtain from saccharose at the present
of bacterium (Leuconostoc mesenteroides). The main type of bond
is α-1,6-glycosidic bond, in place of branching – α-1,4- and α-1,3glycosidic bonds. The average molecular mass of dextranes is few
millions. Partly hydrolyzed dextranes (m. m. – 40000-800000) use in
pharmacy as plasmasubstitute (“Polyglucin”, “Reopolyglucin”).
Inuline
• Inuline – reserve polysaccharide, present in
plants. Inuline has linear structure and
consists of remainders of β-Dfructofuranose, joined by 2,1-glycosidic
bonds, in the end of inuline is α-Dglucopyranose remainder (like saccharose).
Molecular mass of inuline is up to 6000. Use
for obtaining of D-fructose.
Pectin compounds
• Pectin compounds (pectins) –
polysaccharides consist of polygalacturonic
acid, which contain remainders of α-Dgalacturonic acid joined by 1,4glycosidic bonds. Part of carboxyl grups
present in appearance of methyl ether.
Water solutions of pectins form stable
gels. Pectins have antiulcer properties.
Chitin is а polysaccharide that is similar
to cellulose in both function and structure. Its
function is to give rigidity to the exoskeletons
of crabs, lobsters, shrimp, insects, and other
arthropods. It also occurs in the cell walls of
fungi. Structurally, chitin is а linear polymer
(no branching) with all (1- 4) glycosidic
linkages, as in cellulose. Chitin differs from
cellulose in that the monosaccharide present is
an N-acetylamino derivative of D-glucose.
Heteropolysaccharides.
Unlike all the polysaccharides we have discussed up to
this point, mucopolysaccharides are heteropolysaccharides
rather than homopolysaccharides.
• Mucopolysaccharides are compounds that occur in
connective tissue associated with joints in animals and
humans. Their function is primarily that of lubrication, а
necessary requirement if movement is to occur. The name
mucopolysaccharide comes from the highly viscous,
gelatinous (mucus-like) consistency of these substances in
aqueous solution.
• А heteropolysaccharide is а polysaccharide in which more
than one (usually two) type of monosaccharide unit is present.
One of the most common mucopolysaccharides is hyaluronic
acid, а heteropolysaccharide in which the following two
glucose derivatives alternate in the structure.
It is а highly viscous substance and has а molecular weight in
several hundred millions. Hyaluronic acid is а principal component
of the ground substance of connective tissue. Among other places it
is found in skin, synovial fluid, vitreous hemour of the eye, and
umbilical cord. It exercises а cementing function in the tissues and
capillary walls, and forms а coating gel round the ovum. It accounts
for about 80% of the viscosity of synovial fluid which contains
about 0. 02 – 0.05% of hyaluronate. Repeat part of hyaluronic acid
is D-glucuronic acid and N-acetyl-D-glucosamine joined by β1,3-glycosidic bond, between disaccharide fragments – β-1,4.
Molecular mass of hyaluronic acid is from 1600 to 6400.
(1,4)-O--D-Glucopyranosyluronic acid-(1,3)-2-acetamino-2-dezoxy--D-glucopyranose.
Hyaluronic acid is split up by the enzyme
hyalurosidase into а number of small molecule. If
fluid containing this enzyme is injected into а tissue it
spreads rapidly, from the site of injection and thus
this enzyme is sometimes referred as the “spreading
factor”. It is found in relatively high concentration in
the testis and seminal fluid, in the venoms of certain
snakes and insects, and in some bacteria. The enzyme
also has а physiological role in fertilization. The
sperm is rich in the enzyme and the former can thus
advance better in the cervical canal and finally
penetrates the ovum.
Chondroitin sulfate. It has similar structure as hyaluronic acid
with the difference that the N-acetyl-D-glucosamine unit of the
molecule is replaced by N-acetyl-D-galactosamine unit with
sulphate group. Repeat part of chondroitin sulphate is D-glucuronic
acid and N-acetyl-D-galactosamine which contains sulfate group.
Inside of disaccharide fragment is β-1,3-glycosidic bond; between
fragments – β-1,4. Sulfate group forms ether bond with hydroxyl
group of N-acetyl-D-galactosamine in location 4 (chondroitin-4sulfate) or in location 6 (chondroitin-6-sulfate). Chondroitin
sulfates are found in cartilage, bone, heart valves, tendons and
cornea.
(1,4)-O--D-Glucopyranosyluronic acid-(1,3)-2-acetamino-2-dezoxy-6-O-sulfo--Dgalactopyranose.
Hydrocarbon chains of chondroitin-4-sulfate contain
up to 150 disaccharides remainders, joined in
organism by O-glycosidic bonds with hydroxyl groups
of aminoacid remainders.
Dermatan sulfate. (Varying amounts of Dglucuronic acid may be present. Concentration
increases during aging process.)
(1,4)-O--L-idopyranosyluronic acid-(1,3)-2acetamino-2-dezoxy-4-O-sulfo--Dgalactopyranose.
Heparin. It is naturally occurring anticoagulant found mainly
in the liver, and also in lung, spleen, kidney and intestinal mucosa.
It prevents blood clotting by inhibiting the prothrombin-thrombin
conversion and thus eliminating the thrombin effect on fibrinogen.
Repeat part of heparin consists of D-glucosamin and uronic acid,
joined by α-1,4-glycosidic bonds. As uronic acid in heparin present
L-iduronic acid or, very rare, D-glucuronic acid. Remainders of
glucosamine and L-iduronic acid partly sulfonated. Molecular mass
of heparin is 16000-20000.
(1,4)-O--D-idupyranosyluronic acid-2-O-sulfo-(1,4)-2sulfamino-2-dezoxy-6-O-sulfo--D-glucopyranose
5. Glycoconjugates.
The compounds that result from the covalent
linkages of carbohydrate molecules to both proteins
and lipids are collectively known as the
glycoconjugates. These substances have profound
effects on the function of individual cells, as well as
the cell-cell interactions of multicellular organisms.
There are two classes of carbohydrate-protein
conjugate: proteoglycans and glycoproteins.
Although both molecular types contain сагbohydrate
and protein, their structures and functions appear, in
general, to be substantially different. The glycolipids,
which are oligosaccharide-containing lipid molecules,
are found predominantly on the outer surface of
plasma membranes.
Proteoglycans are distinguished from the
common glycoproteins by their extremely high
carbohydrate content, which may constitute as
much as 95% of the dry weight of such
molecules. These molecules are found
predominantly in the extracellular matrix
(intercellular material) of tissues. All
proteoglycans contain GAG chains. The GAG
chains are linked to protein molecules (known as
core proteins) by N- and O-glycosidic linkages.
The diversity of proteoglycans is а result of both
the number of different core proteins and the
large variety of different classes and length of
the carbohydrate chains.
Fig. Proteoglycan structure
Because proteoglycans contain large numbers of GAGs,
which are polyanions, large volumes of water and cations are
trapped within their structure. As а result, proteoglycan
molecules occupy space that is thousands of times bigger that of
а densely packed molecule of the same mass. Proteoglycans
contribute support and elasticity to tissues in which they occur.
Consider, for example, the strength, flexibility, and resilience of
cartilage. The structural diversity of proteoglycans allows them
to serve а variety of structural and functional roles in living
organisms. Proteoglycans are particularly abundant in the
extracellular matrix of connective tissue. Together with matrix
proteins such as collagen, fibrinogen and laminin, they form an
organized meshwork that provides strength and support to
multicellular tissues. Proteoglycans are also present at the
surface of cells, where they are directly bound with the plasma
membrane. Although the function of these latter molecules is
not yet clear, the suggestion has been made that they play an
important role in membrane structure and cell-cell interactions.
А number of genetic diseases associated with proteoglycan
metabolism, known as mucopolysaccharidoses, have been
identified. Because proteoglycans are constantly being
synthesized and degraded, their excessive accumulation (due to
missing or defective lyzosomal enzymes) has very serious
consequences. For example, in Hurler's syndrome, an autosomal
recessive disorder (а disease type in which one copy of the
defective gene is inherited from each parent), deficiency of а
specific enzyme results in accumulation of dermatan sulfate.
Symptoms include mental retardation, skeletal deformity, and
early childhood death. Glycoproteins are commonly defined as
proteins that are covalently linked to carbohydrate through Oor N-linkages. The carbohydrate contain of glycoprotein varies
from 1% to over 85% of total weight. The types of carbohydrate
that are founded include monosaccharides and disaccharides
such as those attached to the structural protein collagen and
branched oligosaccharides on plasma glycoproteins. Although
the glycoproteins are sometimes considered to include the
proteoglycans, there appear to be sufficient structural reasons to
examine them separately.
These substances include glycoproteins of uronic
acids, sulfate groups and disaccharide repeating units
that are typical for proteoglycans. The carbohydrate
groups of glycoproteins are linked to the polypeptide
by either (1) an N-glycosidic linkage between Nacetylglucosamine (GlcNAc) and the aminoacid
asparagine (Asn) or (2) an O-glycosidic linkage
between N-acetylgalactosamine (GalNAc) and the
hydroxyl group of the аminoacids serine (Ser) or
threonine (Thr). The former glycoprotein class is
sometimes referred to as asparagine-linked; the latter
is often called mucin-type.
• Asparagine-linked carbohydrates. As was
mentioned previously, three structural forms of
asparagine-linked oligosaccharide occur in
glycoproteins: high- mannose, complex, and hybrid.
High-mannose type is composed of GlcNAc and
mannose. Complex-type may contain fructose,
galactose, and sialic acid in addition to GlcNAc and
mannose. Hybrid-type oligosaccharides contain
features of both complex and high-mannose-type
species. Despite these differences, the core structure
of all N-linked oligosaccharides is the same. This
core, which is constructed on а membrane-bound
lipid molecule, is covalently linked to asparagine
during protein synthesis. Several additional reactions,
which occur within the lumen of the endoplasmic
reticulum and the Golgi complex, result in the final
N-linked oligosaccharide structures.
Mucin-type carbohydrate While all N-linked
oligosaccharides are bound to protein via GlcNAc-Asn, the
linking groups of O-glycosidic oligosaccharides are of several
types. The most common of these is GalNAc-Ser (or GalNAcThr). Considerable mucin-type carbohydrate unit is
disaccharide such as Gal-1,3-GalNAc, found in the antifreeze
glycoprotein of antarctic fish (Figure), to the complex
oligosaccharides of blood groups such as those of the ABO
system.
Fig. Antifreeze glycoprotein structure.
6. Lipids
Lipids differ from the other classes of naturally occurring
biomolecules (carbohydrates, proteins, and nucleic acids), they
are more soluble in non- or weakly polar solvents (diethyl
ether, hexane, dichloromethane) than in water. They include a
variety of structural types, a collection of which is introduced
in this chapter. In spite of the number of different structural
types, lipids share a common biosynthetic origin in that they
are ultimately derived from glucose. During one stage of
carbohydrate metabolism, called glycolysis, glucose is
converted to lactic acid. Pyruvic acid is an intermediate
product.
Classification of lipids
• Classification: Lipids can be divided into two major classes on the basis of
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•
•
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•
•
whether they undergo hydrolysis reactions in alkaline (basic) solution.
Saponifiable lipids can be hydrolyzed under alkaline conditions to yield
salts of fatty acids. Nonsaponifiable lipids do not undergo hydrolysis
reactions in alkaline solution.
The basis of the nature of the products obtained on hydrolysis lipids are
mainly divided into three type: simple, compound and derived lipids.
1. Simple lipids. These are esters of fatty acids and alcohols and thus on
hydrolysis give fatty acids and alcohols. They may be of two types.
а) Fats and oils. These are esters of fatty acids and glycerol (а trihydric
alcohol). These are also known as glycerides.
b) Waxes. These are esters of long-chain fatty acids and long-chain
monohydric alcohols or sterols.
2 Compound lipids. Compound lipids are esters of fatty acids and alcohols
in combination with other compound and thus on hydrolysis give fatty acids,
alcohol and other compounds. On the basis of the nature of the other
group, compound lipids may again be of following types.
а) Phospholipids. These are fat like compounds containing phosphoric acid
and а nitrogen base.
b) Glycolipids. These are compounds containing а fatty acid, а carbohydrate,
а complex alcohol, and nitrogen, but nо phosphorus.
3. Derived lipids. These compounds although do not contain an ester
linkage but are obtained by the hydrolysis of simple and compound lipids.
They may be fatty acids, alcohols and sterols.
Lipids are organic compounds, found in living
organisms, that are soluble in nonpolar organic solvents.
Because compounds are classified as lipids on the basis of a
physical property— their solubility in an organic solvent—
rather than as a result of their structures, lipids have a
variety of structures and functions, as the following
examples illustrate:
Functions of lipids
– The most important role of lipids is as а fuel. Much of the
carbohydrates of the diet are converted to fat which is stored in
various tissues and utilised at the time of requirement. Thus fat
may be the major source of energy for many tissues. Actually,
in some respects lipids (fats) are even superior to
carbohydrates as source of energy.
– Fatty acids with their flexible backbones can be stored in а
much more compact form than the highly spatially oriented and
rigid glycogen structure. Thus fat storage provides economy in
both weight and space. In addition to the above three reasons
there are two other reasons for fat storage as an excellent form
of energy.
– As it is insoluble in water, it has been carried to the fat
depots by the specialised transport proteins in the plasma.
– It remains as а stable and fixed reserve of energy until
mobilized by enzymes which hydrolyse it to glycerol and fatty
acids. The enzymes are under the control of various hormones
and are activated under conditions where the body is involved
in increased energy expenditure.
– Fat may also provide padding to protect the internal
organs. Brain and nervous tissue are rich in certain
lipids, а fact which indicates the importance of these
compounds to life.
– Some compounds derived from lipids are important
building blocks of biologically active materials; е.g. acetic
acid can be used by the body to synthesize cholesterol
and related compounds (hormones).
– Lipoproteins are constituents of cell walls. The lipids
present in lipoproteins constituting the cell walls are of
the types of phospholipids. Since lipids are water
insoluble they act as ideal barrier for preventing water
soluble materials from passing freely between the intraand extra-cellular fluids.
– One more important function of dietary lipids is that of
supplying the so-called essential fatty acids although
there are several functions (essential fatty acids (EFA),
none of them are well defined.
Fats and oils are naturally occurring mixtures of triacylglycerols,
also called triglycerides.They differ in that fats are solids at room
temperature and oils are liquids. We generally ignore this distinction and
refer to both groups as fats. Triacylglycerols are built on a glycerol
framework.
Simple triacylglycerines include similar fatty acids
,
mixed – different. All three acyl groups in a triacylglycerol
may be the same, all three may be different, or one may be
different from the other two.
Nomenclature, methods of getting
of fats
For simple glycerides the name is made up of the name of the alcohol
(glycerol) or its radical (glyceryl) and the name of the acid; or the name
of the acid concerned is changed to suffix in. For mixed glycerides, the
position and names of the acid groups are specified by Greek letters α, β,
α’ or by the numerals 1, 2 and 3.
Methods of getting:
1. O-acylation of alcohols;
2. Allocation from plants: melting out, pressing or
extraction by organic solvents.
Fatty acids are carboxylic acids with long
hydrocarbon chains. Because they are synthesized
from acetate, a compound with two carbon atoms,
most naturally occurring fatty acids contain an even
number of carbon atoms and are unbranched. Fatty
acids can be saturated with hydrogen (and therefore
have no carbon–carbon double bonds) or unsaturated
(have carbon–carbon double bonds). Fatty acids with
more than one double bond are called
polyunsaturated fatty acids. Double bonds in
naturally occurring unsaturated fatty acids are never
conjugated — they are always separated by one
methylene group. The physical properties of a fatty
acid depend on the length of the hydrocarbon chain
and the degree of unsaturation. As expected, the
melting points of saturated fatty acids increase with
increasing molecular weight because of increased
Van-der-Waals interactions between the molecules
The most widespread fatty acids in
natural oils and fats:
Double bonds are rigid structures, unsaturared acid molecules that
contain them can occur in two isomeric forms: cis and trans. In cis-isomers,
for example, similar or identical groups are on the same side of double
bond (a). When such groups are on opposite sides of a double bond, the
molecule is said to be a trans-isomer (b):
The double bonds in unsaturated fatty acids generally have the cis
configuration. This configuration produces a bend in the molecules, which
prevents them from packing together as tightly as fully saturated fatty
acids. As a result, unsaturated fatty acids have fewer intermolecular
interactions and, therefore, lower melting points than saturated fatty acids
with comparable molecular weights . The melting points of the unsaturated
fatty acids decrease as the number of double bonds increases. For example,
an 18-carbon fatty acid melts at 69 °C if it is saturated, at 13 °C if it has one
double bond, at if it has two -5 °C o double bonds, and at -11 °C if it has
three double bonds.
Triacylglycerols, also called triglycerides,
are compounds in which the three OH-groups
of glycerol are esterified with fatty acids. If the
three fatty acid components of a triacylglycerol
are the same, the compound is called a simple
triacylglycerol. Mixed triacylglycerols, on
the other hand, contain two or three different
fatty acid components and are more common
than simple triacylglycerols. Not all
triacylglycerol molecules from a single source
are necessarily identical; substances such as
lard and olive oil, for example, are mixtures of
several different triacylglycerols.
Triacylglycerols that are solids or semisolids at room temperature
are called fats. Fats are usually obtained from animals and are composed
largely of triacylglycerols with either saturated fatty acids or fatty acids
with only one double bond. The saturated fatty acid tails pack closely
together, giving the triacylglycerols relatively high melting points, causing
them to be solids at room temperature. Liquid triacylglycerols are called
oils. Oils typically come from plant products such as corn, soybeans,
olives, and peanuts. They are composed primarily of triacylglycerols with
unsaturated fatty acids that cannot pack tightly together. Consequently,
they have relatively low melting points, causing them to be liquids at
room temperature.
Hydrolysis of а triacylglycerol
Hydrolysis of а triacylglycerol is the
reverse of the esterification reaction by
which it wet formed. Complete hydrolysis
of а triacylglycerol molecule always gives
one glycerol molecule and three fatty acid
molecules as products.
7. Chemical properties of fats
1). Hydrolysis of fats with alkali (e.g., sodium hydroxide) yields salts of the
fatty acids, and those of the alkali metals, such as sodium or potassium, are
useig as soaps. Another name of this reaction – “saponification”:
The solubility of lipids in nonpolar organic solvents results from their
significant hydrocarbon component. The hydrocarbon portion of the
compound is responsible for its “oiliness” or “fattiness.” The word lipid
comes from the Greek lipos, which means “fat.”
Characterization of fats. The composition, quality and purity of а given oil
or fat is determined by means of а number of physical and chemical tests. The
usual physical tests include determination of m, р, specific gravity, viscosity,
etc. while the chemical tests include determination of certain values discussed
below.
• 1. Acid number. It is the number of milligrams of potassium
hydroxide required to neutralise the free fatty acids in 1g. of the oil
or fat. Thus it indicates the amount of free fatty acids present in oil
or fat. А high acid value indicates а stale oil or fat stored under
improper conditions.
• 2. Saponification number. It is number of milligrams of
potassium hydroxide required to completely hydrolysis of l g. of the
oil or fat. Thus it is а measure of fatty acids present as esters in а
given oil or fat. The saponification value gives an idea about the
molecular weight of fat or oil. The saponification number and
molecular weight of an oil are inversely proportional to each other;
thus high saponification number indicates that the fat is made up of
low molecular weight fatty acids and vice versa. It is also helpful in
detecting adulteration of а given fat by one of the lower or higher
saponfication value.
• 3. Iodine number. It is the number of grams of iodine that
combine with 100 g. of oil or fat. It is а measure of the degree of
unsaturation of а fat or oil; а high iodine number indicates а high
degree of unsaturation of the fatty acids of the fat.
• Difference between saponification and acid numbers named ether
number which characterizes contain of the remainders of fatty
2). Oxidation of fates.
Oxidation cases rancidity of fates.
During oxidation form aldehydes with short carbon chain.
Oxidation at the soft conditions (water solution of
KMnO4) cases formation of glycols. At the rigid
conditions carbon skeleton destroys with formation of
remainders of carbonic acids with shorter carbon
chains.
Fats, which predominantly contain saturated fatty acids, by
oxidation form ketones.
3). Hydrogenation.
Some or all of the double bonds of
polyunsaturated oils can be reduced by catalytic hydrogenation. Margarine
and shortening are prepared by hydrogenating vegetable oils such as soybean
oil and sunflower oil until they have the desired consistency. This process is
called “hardening of oils.” The hydrogenation reaction must be carefully
controlled, however, because reducing all the carbon–carbon double bonds
would produce a hard fat with the consistency of beef tallow. Quantity of H2 in
grams, which are necessary for hydration of 10kg of fats (hydration
number) characterizes unsaturating of fat.
4). Addition of halogens.
Iodine number for plants fats – 100-200, for
animal fats – 25-86, for fish fats – 100-193.
As might be expected from the properties of the fatty acids, fats
have a predominance of saturated fatty acids, and oils are composed
largely of unsaturated acids. Thus, the melting points of triglycerides
reflect their composition, as shown by the following examples. Natural
mixed triglycerides have somewhat lower melting points, the melting
point of lard being near 30 º C, whereas olive oil melts near -6 º C.
Since fats are valued over oils by some Northern European and North
American populations, vegetable oils are extensively converted to solid
triglycerides (e.g. Crisco) by partial hydrogenation of their
unsaturated components. Some of the remaining double bonds are
isomerized (to trans) in this operation. These saturated and trans-fatty
acid glycerides in the diet have been linked to long-term health issues
such as atherosclerosis.
8. Phospholipids. Waxes.
Triacylglycerols arise, not by acylation of glycerol itself,
but by a sequence of steps in which the first stage is acyl
transfer to L-glycerol 3-phosphate (from reduction of
dihydroxyacetone 3-phosphate, formed as described in Section
25.21). The product of this stage is called a phosphatidic
acid.
Hydrolysis of the phosphate ester function of the
phosphatidic acid gives a diacylglycerol, which then reacts
with a third acyl coenzyme A molecule to produce a
triacylglycerol. Phosphatidic acids not only are intermediates in
the biosynthesis of triacylglycerols but also are biosynthetic
precursors of other members of a group of compounds called
phosphoglycerides or glycerol phosphatides. Phosphoruscontaining derivatives of lipids are known as phospholipids, and
phosphoglycerides are one type of phospholipid. One important
phospholipid is phosphatidylcholine, also called lecithin.
Phosphatidylcholine is a mixture of diesters of phosphoric acid.
An animated display of micelle formation is
presented below. Notice the brownish material in the
center of the three-dimensional drawing on the left.
This illustrates a second important factor contributing
to the use of these amphiphiles as cleaning agents.
Micelles are able to encapsulate nonpolar 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 nonpolar 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. If the animation
has stopped, it may be restarted by clicking on it.
Classification of phospholipids
The oldest amphiphilic cleaning agent known to humans is
soap. Soap is manufactured by the base-catalyzed hydrolysis
(saponification) of animal fat (see below). 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 salts in the water supply (hard water). These
divalent cations cause aggregation of the micelles, which then
deposit as a dirty scum.
Washing action of soaps
Waxes
Waxes are water-repelling solids that are part of the
protective coatings of a number of living things, including the
leaves of plants, the fur of animals, and the feathers of birds.
They are usually mixtures of esters in which both the alkyl and
acyl group are unbranched and contain a dozen or more carbon
atoms. Beeswax, for example, contains the ester triacontyl
hexadecanoate as one component of a complex mixture of
hydrocarbons, alcohols, and esters.
• Wax is а mixture of esters of high molecular weight
•
•
alcohols and high molecular weight fatty acids.
Waxes are saроinfied with great difficulty than fats
and are not attacked by lipase. Although waxes may
be saponified by prolonged boiling with alcoholic KOH,
they are more easily saponified by treating а solution
of the wax in petroleum ether with absolute alcohol
and metallic sodium, with sodium ethoxide. The
saponification products оf waxes are water-soluble
soaps (sodium »Its of higher fatty acids); while the
water insoluble long-chain alcohols appear in the
"unsaponifiable matter" fraction. Waxes contain about
31 -55% of the unsaponifiable matter, while fats and
oils contain only 1 - 2% unsaponifiable matter.
Waxes dividing on animal’s (spermaceti, bees wax,
lanoline and others) and plants (carnauba wax).
• Bees wax. It contains esters derived from alcohols having 24
•
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•
•
•
- 30 carbon atoms, include palmitate of miriсуl alcohol
(С30H61ОН) and n-hexacosanol (С26Н53ОН).
СН3(CН2)14COOC30H61
СН3 (CН2)14COOC26H53
miricyl patmitate
n- hexacosanyl patmitate
Spermaceti. It is obtained from the head of the sperm whale.
It is rich in ester of cetyl alcohol (С16Н33ОН) and palmitinic
acid: СН3 (C Н2 ) 14COOC16H33 - cetyl palmitate
Spermaceti is used in making of candles.
Sperm Oil. It is а liquid wax and occurs with spermaceti in
the sperm whale. It is а valuable lubricant used for delicate
instruments, such as watches. It does not become gummy, as
many oils do.
Carnauba wax. It is found in the leaves of the carnauba
palm of Brazil. It is used as an ingredient in the manufacture
of various wax polishes. Because waxes are very inert
chemically, they make an excellent protective coating.
Lanolin or wool wax. It is obtained from wool and is used in
making ointments and salves.
9. Nonsaponifiable lipids
1). Prostaglandins – physiologically active
substances with biogenic origin, stimulate
smooth muscles and lowers blood
pressure. All prostaglandins contain
carboxyl group and 20 carbon atoms in
molecule, they are derivatives of
eyicosanic acid.
Research in physiology carried out in the 1930s
established that the lipid fraction of semen contains
small amounts of substances that exert powerful
effects on smooth muscle. Sheep prostate glands
proved to be a convenient source of this material and
yielded a mixture of structurally related substances
referred to collectively as prostaglandins. We now
know that prostaglandins are present in almost all
animal tissues, where they carry out a variety of
regulatory functions. Prostaglandins are extremely
potent substances and exert their physiological effects
at very small concentrations. Because of this, their
isolation was difficult, and it was not until 1960 that
the first members of this class, designated PGE1 and
PGF1, were obtained as pure compounds.
All the prostaglandins are 20-carbon carboxylic acids
and contain a cyclopentane ring. All have hydroxyl groups at C11 and C-15 (for the numbering of the positions in
prostaglandins). Prostaglandins belonging to the F series have
an additional hydroxyl group at C-9, and a carbonyl function is
present at this position in the various PGEs. The subscript
numerals in their abbreviated names indicate the number of
double bonds. Prostaglandins are believed to arise from
unsaturated C20-carboxylic acids such as arachidonic acid.
Mammals cannot biosynthesize arachidonic acid directly.
They obtain linoleic acid from vegetable oils in
their diet and extend the carbon chain of linoleic acid
from 18 to 20 carbons while introducing two more
double bonds. Linoleic acid is said to be an essential
fatty acid, forming part of the dietary requirement of
mammals. Animals fed on diets that are deficient in
linoleic acid grow poorly and suffer a number of
other disorders, some of which are reversed on
feeding them vegetable oils rich in linoleic acid and
other polyunsaturated fatty acids. One function of
these substances is to provide the raw materials for
prostaglandin biosynthesis.
Physiological responses to prostaglandins
encompass a variety of effects. Some prostaglandins
relax bronchial muscle, others contract it. Some
stimulate uterine contractions and have been used to
induce therapeutic abortions. PGE1 dilates blood
vessels and lowers blood pressure; it inhibits the
aggregation of platelets and offers promise as a drug
to reduce the formation of blood clots. The longstanding question of the mode of action of aspirin has
been addressed in terms of its effects on
prostaglandin biosynthesis. Prostaglandin
biosynthesis is the body’s response to tissue damage
and is manifested by pain and inflammation at the
affected site. Aspirin has been shown to inhibit the
activity of an enzyme required for prostaglandin
formation. Aspirin reduces pain and inflammation—
and probably fever as well—by reducing
prostaglandin levels in the body.
Much of the fundamental work on prostaglandins
and related compounds was carried out by Sune
Bergström and Bengt Samuelsson of the Karolinska
Institute (Sweden) and by Sir John Vane of the
Wellcome Foundation (Great Britain). These three
shared the Nobel Prize for physiology or medicine in
1982. Bergström began his research on
prostaglandins because he was interested in the
oxidation of fatty acids. That research led to the
identification of a whole new class of biochemical
mediators. Prostaglandin research has now revealed
that other derivatives of oxidized polyunsaturated
fatty acids, structurally distinct from the
prostaglandins, are also physiologically important.
These fatty acid derivatives include, for example, a
group of substances known as the leukotrienes,
which have been implicated as mediators in
immunological processes.
Prostaglandins have cyclopentane ring. According to allocation of double
bonds in fivemember cycle and side chains prostaglandins marked by
litters A, B, C, D, E and F.
According to the number of double bonds in side chains every group of
prostaglandins divided on series that marked as indexes.
In the names of prostaglandins orientation of hydroxyl
group in location 9 according to the carbon chain at
C8 mark α or β. α – means cis-configuration, β –
trance.
2). Isoprenoides – products of isoprene
transformation. Some vitamins and hormones have
isoprenoides structure.
Isoprenoides includes terpens, carotinoids and steroids
10. Terpenes and terpenoids. Terpene
biosynthesis.
A terpene is a naturally occurring hydrocarbon
based on combinations of the isoprene unit.
Terpenoids are compounds related to terpenes, which
may include some oxygencontaining derivatives
(alcohols, aldehydes and ketones), however the two
terms are often used interchangeably.
Terpenes are a large and varied class of
hydrocarbons, produced primarily by a wide variety
of plants, particularly conifers, though also by some
insects such as termites or swallowtail butterflies,
which emit terpenes from their osmeterium. They are
the major components of resin, and of turpentine
produced from resin.
The name "terpene" is derived from the word
"turpentine". In addition to their roles as end-products in many
organisms, terpenes are major biosynthetic building blocks
within nearly every living creature. Steroids, for example, are
derivatives of the triterpene squalene. When terpenes are
modified chemically, such as by oxidation or rearrangement of
the carbon skeleton, the resulting compounds are generally
referred to as terpenoids. Some authors will use the term
terpene to include all terpenoids. Terpenoids are also known as
isoprenoids. Terpenes and terpenoids are the primary
constituents of the essential oils of many types of plants and
flowers. Essential oils are used widely as natural flavor
additives for food, as fragrances in perfumery, and in
traditional and alternative medicines such as aromatherapy.
Synthetic variations and derivatives of natural terpenes and
terpenoids also greatly expand the variety of aromas used in
perfumery and flavors used in food additives. Vitamin A is an
example of a terpene.
Terpene biosynthesis.
The reaction of dimethylallyl
pyrophosphate with isopentenyl pyrophosphate
forms geranyl pyrophosphate, a 10-carbon
compound. In the first step of the reaction,
isopentenyl pyrophosphate acts as a
nucleophile and displaces a pyrophosphate
group from dimethylallyl pyrophosphate.
Pyrophosphate is an excellent leaving group:
Its four OH-groups. Therefore, three of the
four groups will be primarily in their basic
forms at physiological pH A proton is removed
in the next step, resulting in the formation of
geranyl pyrophosphate.
The following scheme shows how some of the many
monoterpenes could be synthesized from geranyl
pyrophosphate:
11. Classification of terpenes.
Terpenes may be classified by the number of
terpene units in the molecule; a prefix in the name
indicates the number of terpene units needed to
assemble the molecule. A single terpene unit is
formed from two molecules of isoprene, so that a
monoterpene consists of one terpene but two isoprene
units.
Hemiterpenes consist of a single isoprene unit.
Isoprene itself is considered the only hemiterpene, but
oxygen-containing derivatives such as prenol and
isovaleric acid are hemiterpenoids.
Monoterpenes consist of two isoprene units and
have the molecular formula C10H16. Examples of
monoterpenes are: geraniol, limonene and terpineol.
Sesquiterpenes consist of three isoprene units and have
the molecular formula C15H24. Examples of
sesquiterpenes are: farnesenes, farnesol. The sesquiprefix means one and a half.
Diterpenes are composed for four isoprene units and
have the molecular formula C20H32. They derive from
geranylgeranyl pyrophosphate. Examples of diterpenes
are cafestol, kahweol, cembrene and taxadiene
(precursor of taxol). Diterpenes also form the basis for
biologically important compounds such as retinol,
retinal, and phytol. They are known to be antimicrobial
and antiinflammatory.
Sesterterpenes, terpenes having 25 carbons and five
isoprene units, are rare relative to the other sizes. The
sester- prefix means half to three, i.e. two and a half.
Examples of sesterterpenes are geranylfarnesol.
Triterpenes consist of six isoprene units and have the
molecular formula C30H48. The linear triterpene
squalene, the major constituent of shark liver oil, is
derived from the reductive coupling of two molecules of
farnesyl pyrophosphate. Squalene is then processed
biosynthetically to generate either lanosterol or
cycloartenol, the structural precursors to all the steroids.
Tetraterpenes contain eight isoprene units and have the
molecular formula C40H64. Biologically important
tetraterpenes include the acyclic lycopene, the
monocyclic gamma-carotene, and the bicyclic α- and βcarotenes.
Polyterpenes consist of long chains of many isoprene
units. Natural rubber consists of polyisoprene in which
the double bonds are cis. Some plants produce a
polyisoprene with trans double bonds, known as guttapercha
Classification of terpenes
The higher terpenes are formed not by successive addition
of C5 units but by the coupling of simpler terpenes. Thus, the
triterpenes (C30) are derived from two molecules of farnesyl
pyrophosphate, and the tetraterpenes (C40) from two molecules
of geranyl pyrophosphate. These carbon–carbon bond-forming
processes involve tail-to-tail couplings and proceed by a more
complicated mechanism than that just described. The enzymecatalyzed reactions that lead to geraniol and farnesol (as their
pyrophosphate esters) are mechanistically related to the acidcatalyzed dimerization of alkenes. The reaction of an allylic
pyrophosphate or a carbocation with a source of electrons is a
recurring theme in terpene biosynthesis and is invoked to
explain the origin of more complicated structural types.
Consider, for example, the formation of cyclic monoterpenes.
Neryl pyrophosphate, formed by an enzyme-catalyzed
isomerization of the E double bond in geranyl pyrophosphate,
has the proper geometry to form a six-membered ring via
intramolecular attack of the double bond on the allylic
pyrophosphate unit.
Loss of a proton from the tertiary carbocation formed in this step gives
limonene, an abundant natural product found in many citrus fruits. Capture of
the carbocation by water gives -terpineol, also a known natural product.
Monoterpens
They are the terpenes that have been known for several
centuries as components of the fragrant oils obtained from
leaves, flowers and fruits. Monoterpenes, with sesquiterpenes,
are the main constituents of essential oils.
Acyclic monoterpens:
They can be considered as derivatives of 2,6-dimethyloctane.
In the basis of carbon skeleton acyclic monoterpens
are structures of isoprene isomeric dimers: myrcene
and ocimene.
Geraniol and nerol alcohols are derivatives of carbohydrates
monoterpens. Geraniol has cis-form and nerol – trance-form.
Among natural molecules, the followings are well
known and have several structural isomers.
Geraniol and citral present in ether oils, especially in citric oil. They are
pheromones.
Monocyclic monoterpenes
They are derived from cyclohexane with an isopropyl substituent. The
most important members are limonene and methane.
Limonene (dipentene) can be obtained by isoprene isomerisation with
heating to 150 C in soldered ampoule. At 500-700 C reverse processes
takes place.
– Catalytically hydrogenisation of limonene
– hydratation of limonene:
Menthane (1-isopropilmethylbenzol) is obtained from p-cimol (nisopropilmethylbenzol) hydration.
From hydroxyderivatives of menthane most important is menthol
(menthanol-3), which has tree asymmetric centers. (-)Menthol
synthesized by reducing of menthon.
Menthol has antiseptic,
sedative, analgesic
properties (Boromenthol,
Pectussine)
(+)Menthol in industry synthesized by alkylation of m-crezol with following hydration
of tymol.
Terpinehydrate (monohydrate menthandiol-1,8)
use in medicine in treatment of chronic
bronchitis.
Bicyclic monoterpenes:
The same tertiary carbocation serves as the precursor to
numerous bicyclic monoterpenes. A carbocation having a bicyclic
skeleton is formed by intramolecular attack of the electrons of the
double bond on the positively charged carbon. In the basis of
bicyclic monoterpenes are four cyclic terpenic carbohydrates:
α-Pinene contains in turpentine oil – turpentine
(up to 75 %).
Heating with dilute acids (H2SO4, HNO3):
After oxidation on air forms verbenon:
Borneol – alcohol of bornane (camphane) chain:
Isoborneol is borneol’s diastereomer:
Synthesis of difficult esters of borneol
Oxidation by chromic acid:
Interaction between borneol and acids:
Camphene can hydrolyze in acidic medium with
formation of isoborneol.
Camphor – bicyclic ketone, has two asymmetric atoms,
but dosen’t have diastereomers.
Camphor uses for stimulation of
respiratory and vesselmoving
centers, has antiseptic properties,
stimulates metabolite processes.
Tishchenko synthesis
Methylene group in α-location (according to carbonyl group) has CHacidic properties.
Oxidation of camphor with nitrate acid
12. Carotenoids.
Carotenoids are natural pigments characterized
by a tail-to-tail linkage between two C20 units and an
extended conjugated system of double bonds. They are
the most widely distributed of the substances that give
color to our world and occur in flowers, fruits, plants,
insects, and animals. It has been estimated that
biosynthesis from acetate produces approximately a
hundred million tons of carotenoids per year. The most
familiar carotenoids are lycopene and -carotene,
pigments found in numerous plants and easily isolable
from ripe tomatoes and carrots, respectively.
Carotene – yellow-red pigment, contains in
carrot, milk and butter. Carotene is a mixture
of tree isomers – α-, β- and γ-carotene.
Carotenoids absorb visible light and dissipate its energy as
heat, thereby protecting the organism from any potentially harmful
effects associated with sunlight-induced photochemistry. They are
also indirectly involved in the chemistry of vision, owing to the fact
that -carotene is the biosynthetic precursor of vitamin A, also known
as retinol, a key substance in the visual process.
13. Steroids.
Hormones are chemical messengers—organic compounds
synthesized in glands and delivered by the bloodstream to target
tissues in order to stimulate or inhibit some process. Many
hormones are steroids. Because steroids are nonpolar compounds,
they are lipids. Their nonpolar character allows them to cross cell
membranes, so they can leave the cells in which they are
synthesized and enter their target cells. All steroids contain a
tetracyclic ring system. The four rings are designated A, B, C, and
D. A, B, and C are six-membered rings and D is a five-membered
ring. The carbons in the steroid ring system are numbered as
shown. We have seen that rings can be trans fused or cis fused
and that trans fused rings are more stable. In steroids, the B, C,
and D rings are all trans fused. In most naturally occurring
steroids, the A and B rings are also trans fused.
Classification of steroids.
Some of the common categories of steroids:
Animal steroids
– Insect steroids
• Ecdysteroids such as ecdysterone
– Vertebrate steroids
• Steroid hormones
– Sexual steroids are a subset of sex hormones that produce sex differences or
support reproduction. They include androgens, estrogens, and progestagens.
– Corticosteroids include glucocorticoids and mineralocorticoids.
Glucocorticoids regulate many aspects of metabolism and immune function,
whereas mineralocorticoids help maintain blood volume and control renal
excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids.
– Anabolic steroids are a class of steroids that interact with androgen receptors
to increase muscle and bone synthesis. There are natural and synthetic
anabolic steroids. In popular language, the word "steroids" usually refers to
anabolic steroids.
• Cholesterol, which modulates the fluidity of cell membranes and is the principal
constituent of the plaques implicated in atherosclerosis.
Plant steroids
– Phytosterols
– Brassinosteroids
Fungus steroids
– Ergosterols
Many steroids have methyl groups at the 10- and
13-positions. These are called angular methyl
groups. When steroids are drawn, both angular
methyl groups are shown to be above the plane of the
steroid ring system. Substituents on the same side of
the steroid ring (above the ring) system as the
angular methyl groups are designated β-substituents
(indicated by a solid wedge). Those on the opposite
side of the plane of the ring system (below the ring)
are α-substituents (indicated by a hatched wedge).
Steroids contain sterines, bile acids, steroid hormones,
aglycones of heart glycosides, aglycones of steroid
saponines.
Sterines (sterols) – steroid alcohols, which contain in
basis structure cholestane. Sterines are 3hydroxyderivatives of cholestane, may have one or few
double bonds. Divided on animal sterines (zoosterines),
plant sterines (phytosterines) and sterines of mushrooms
(mycosterines).
The most abundant member of the steroid family in animals is cholesterol
(cholesterine, cholestene-5-ol-3β) , the precursor of all other steroids.
Cholesterol is biosynthesized from squalene, a triterpene. Cholesterol is an
important component of cell membranes .Its ring structure makes it more rigid
than other membrane lipids. Because cholesterol has eight asymmetric carbons,
256 stereoisomers are possible, but only one exists in nature.
The steroid hormones can be divided into five classes: glucocorticoids,
mineralocorticoids, androgens, estrogens, and progestins. Glucocorticoids and
mineralocorticoids are synthesized in the adrenal cortex and are collectively
known as adrenal cortical steroids. All adrenal cortical steroids have an
oxygen at C-11.
• In lipids of human skin cholesteol transforms in vitamin D3
(cholecalciferrol) at the presents of UF-light.
Ergosterine (ergosterol, 24-methylcholestanetrien-5,7,22-ol-3β) refers
to mycosterine group. At the presents of UF-light ergosterol isomerizes in
vitamin D2 (ergocalciferrol)
Bile acids
Bile acids produce by liver from cholesterine and are
hydroxyderivatives of cholanic acid.
In human bile present 4 bile
acids, more popular are cholic
and dezoxycholic acids.
•
In addition to being the precursor of all the steroid
hormones in animals, cholesterol is the precursor of the bile
acids. In fact, the word cholesterol is derived from the Greek
words chole meaning “bile” and stereos meaning “solid.” The
bile acids—cholic acid and dezoxycholic acid—are
synthesized in the liver, stored in the gallbladder,and secreted
into the small intestine, where they act as emulsifying agents
so that fats and oils can be digested by water-soluble digestive
enzymes. Cholesterol is also the precursor of vitamin D.
Bile acids exist in organism in connection with glycine
aminoacid NH2CH2COOH or taurine NH2CH2CH2SO3H.
Steroid hormones
• Steroid hormones include corticosteroids and
sexual hormones. Corticosteroids produce in the
bark of adrenal glands, they are derivatives of
pregnane and divided into glucocorticoids and
mineralocorticoids.
Glucocorticoids, as their name suggests, are
involved in glucose metabolism, as well as in the
metabolism of proteins and fatty acids. Cortisone is
an example of a glucocorticoid. Because of its antiinflammatory effect, it is used clinically to treat
arthritis and other inflammatory conditions. Most
important glucocorticoids are hydrocortisone and
cortisone:
• Mineralocorticoids cause increased
reabsorption of HCO3
• control the balance of Na+, К+, Cl- ions in
cells and balance of water in the kidneys, take
part in regulation of blood pressure.
Aldosterone is an example of a
mineralocorticoid.
• Most important mineralcorticoids are
aldosterone and dezoxycorticosterone:
• In medicine also use synthetic analogs of
hydrocortisone and cortisone –
prednisolone, prednisone,
dexamethasone, triamcinolone. These
substances are more active then natural
corticosteroids.
The sexual hormones can be classified into three major groups:
• 1. Estrogens — the female sexual hormones
• 2. Androgens — the male sexual hormones
• 3. Progestins (gestagenes) — the pregnancy hormones
• The male sexual hormones, known as androgens are secreted
by the testes, estrogens – female sexual hormones are secreted
by the follicles in ovaries, pregnancy hormones form in yellow
body of ovaries.
They are responsible for the development of male secondary
sexual characteristics during puberty. They also promote
muscle growth. Testosterone and androsterone are androgens.
Synthetic steroid with androgen properties – methyltestosterone.
• Estrogens are synthesized in the ovaries and adrenal
•
•
cortex and are responsible for the development of
female secondary sex characteristics at the onset of
puberty and for regulation of the menstrual cycle. They
also stimulate the development of the mammary glands
during pregnancy and induce estrus (heat) in animals.
Androgens are synthesized in the testes and adrenal
cortex and promote the development of secondary male
characteristics. They also promote muscle growth.
Progestins are synthesized in the ovaries and the
placenta and prepare the lining of the uterus for
implantation of the fertilized ovum. They also suppress
ovulation.
Estradiol and estrone (folliculine) are female sexual hormones known as
estrogens. They are secreted by the ovaries and are responsible for the
development of female secondary sex characteristics. They also regulate the
menstrual cycle. Progesterone is the hormone that prepares the lining of the
uterus for implantation of an ovum and is essential for the maintenance of
pregnancy. It also prevents ovulation during pregnancy.
Although the various steroid hormones have remarkably
different physiological effects, their structures are quite similar.
For example, the only difference between testosterone and
progesterone is the substituent at C-17, and the only difference
between androsterone and estradiol is one carbon and six
hydrogens, but these compounds make the difference between
being male and being female. These examples illustrate the
extreme specificity of biochemical reactions.
Synthetic unsteroid estrogens widely use in pharmacy then
steroid estrogens:
Progestins (gestagenes) — the pregnancy hormones,
hormones of yellow body. Maine hestagene hormone
is progesterone.
Aglycones of heart glycosides
• Heart glycosides in big doses very poisoned substances, in small – has
cardiotonic action. Heart glycosides according to its chemical structure are
O-glycosides, in which aglycone has steroid origin, carbohydrate fragment
represent by remainders of mono-, di-, tri- or tetrasaccharides.
• According to the character of lactone cycle heart glycosides divided on two
groups:
1). Cardenolids – contain at C17 fivemember unsaturated lactone cycle;
2). Buphadienolids – contain at C17 sixmember unsaturated lactone cycle;
Carbohydrate fragment can be represent by D-glucose, Dfructose, D-xylose, D-ramnose and also by
methylpentoses:
Heart glycosides of cardenolid group very often
contain as aglycones next compounds:
Example of such heart glycosides is
purpureaglycoside A
Aglycones of steroid saponines
Saponines – group of plant glycosides with high
surface activity, cases hemolysis of erythrocytes.
According to its chemical structure they are Oglycosides, in which aglycone has steroid or
triterpenoid origin. Most aglycones of steroid
saponines contain spiroketal fragment.
14. Properties of cholesterol.
Biosynthesis of cholesterol.
Cholesterol and heart disease.
Cholesterol is probably the best-known lipid
because of the correlation between cholesterol levels
in the blood and heart disease. Cholesterol is
synthesized in the liver and is also found in almost all
body tissues. Cholesterol is also found in many foods,
but we do not require it in our diet because the body
can synthesize all we need. A diet high in cholesterol
can lead to high levels of cholesterol in the
bloodstream, and the excess can accumulate on the
walls of arteries, restricting the flow of blood. This
disease of the circulatory system is known as
atherosclerosis and is a primary cause of heart
disease. Cholesterol travels through the bloodstream
packaged in particles that also contain cholesterol
esters, phospholipids, and proteins.
The particles are classified according to their density.
LDL (lowdensity lipoprotein) particles transport
cholesterol from the liver to other tissues. Receptors on
the surfaces of cells bind LDL particles,allowing them to
be brought into the cell so that it can use the cholesterol.
HDL (high-density lipoprotein) is a cholesterol scavenger,
removing cholesterol from the surfaces of membranes and
delivering it back to the liver, where it is converted into
bile acids. LDL is the so-called bad cholesterol, whereas
HDL is the “good” cholesterol. The more cholesterol we
eat, the less the body synthesizes. But this does not mean
that the presence of dietary cholesterol has no effect on
the total amount of cholesterol in the bloodstream,
because dietary cholesterol also inhibits the synthesis of
the LDL receptors. So the more cholesterol we eat, the
less the body synthesizes, but also, the less the body can
get rid of by bringing it into target cells.
Statins are the newest class of cholesterolreducing drugs. Statins reduce serum cholesterol
levels by inhibiting the enzyme that catalyzes the
reduction of hydroxymethylglutaryl- CoA to
mevalonic acid. Decreasing the mevalonic acid
concentration decreases the isopentenyl
pyrophosphate concentration, so the biosynthesis of
all terpenes, including cholesterol, is diminished. As a
consequence of diminished cholesterol synthesis in
the liver, the liver expresses more LDL receptors—
the receptors that help clear LDL from the
bloodstream.
Studies show that for every 10% that cholesterol is
reduced, deaths from coronary heart disease are reduced by
15% and total death risk is reduced by 11%. Compactin
and lovastatin are natural statins used clinically under the
trade names Zocor® and Mevacor® . Atorvastatin
(Lipitor)®, a synthetic statin, is now the most popular
statin. Lipitor® has greater potency and a longer half-life
than natural statins have, because its metabolites are as
active as the parent drug in reducing cholesterol levels.
Therefore, smaller doses of the drug may be administered.
The required dose is reduced further because is marketed as
a single enantiomer. In addition, it is more lipophilic than
compactin and lovastatin, so it has a greater tendency to
remain in the endoplasmic reticulum of the liver cells,
where it is needed.
Biosynthesis of cholesterol.
How is cholesterol, the precursor of all the steroid
hormones, biosynthesized? The starting material for
the biosynthesis is the triterpene squalene, which
must first be converted to lanosterol. Lanosterol is
converted to cholesterol in a series of 19 steps. The
first step in the conversion of squalene to lanosterol is
epoxidation of the 2,3-double bond of squalene.
Acid-catalyzed opening of the epoxide initiates a
series of cyclizations resulting in the protosterol
cation. Elimination of a C-9 proton from the cation
initiates a series of 1,2-hydride and 1,2-methyl shifts,
resulting in lanosterol.
Synthetic Steroids
The potent physiological effects of steroids led
scientists, in their search for new drugs, to synthesize
steroids that are not available in nature and to
investigate their physiological effects. Stanozolol and
Dianabol are drugs developed in this way. They have
the same muscle-building effect as testosterone.
Steroids that aid in the development of muscle are
called anabolic steroids. These drugs are available
by prescription and are used to treat people suffering
from traumas accompanied by muscle deterioration.
The same drugs have been administered to athletes
and racehorses to increase their muscle mass.
Stanozolol was the drug detected in several athletes in
the 1988 Olympics. Anabolic steroids, when taken in
relatively high dosages, have been found to cause
liver tumors, personality disorders, and testicular
atrophy.
Many synthetic steroids have been found to be much more potent than
natural steroids. Norethindrone, for example, is better than progesterone in
arresting ovulation. Another synthetic steroid, RU 486, when taken along with
prostaglandins, terminates pregnancy within the first nine weeks of gestation.
Notice that these oral contraceptives have structures similar to that of rogesterone.
15. Vitamins.
A vitamin is a substance the body cannot
synthesize that is needed in small amounts for normal
body function. Sir Frederick Hopkins was the first to
suggest that diseases such as rickets and scurvy might
result from the absence of substances in the diet that
are needed only in very small quantities. Because the
first such compound recognized to be essential in the
diet was an amine, Casimir Funk incorrectly
concluded that all such compounds were amines and
called them vitamines (“life-amines”). The e was later
dropped from the name.
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
recommended daily allotment (RDA) of vitamin C is 100 mg, and
amounts as large as 2 to 3 g are taken by many people without
adverse effects. The lipid soluble vitamins, shown in the diagram
below, are not as easily eliminated and may accumulate to toxic
levels if consumed in large quantity. The RDA for these vitamins
are:
Vitamin A 800 μg ( upper limit ca. 3000 μg)
Vitamin D 5 to 10 μg ( upper limit ca. 2000 μg)
Vitamin E 15 mg ( upper limit ca. 1 g)
Vitamin K 110 μg ( upper limit not specified)
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.
16. Water-soluble vitamins.
Thiamine
Thiamine is a colorless compound with a chemical formula
C12H17N4OS. Its structure contains a pyrimidine ring and a thiazole
ring linked by a methylene bridge. Thiamine is soluble in water,
methanol, and glycerol and practically insoluble in acetone, ether,
chloroform, and benzene. It is stable at acidic pH, but is unstable in
alkaline solutions. Thiamine is unstable to heat, but stable during
frozen storage. It is unstable when exposed to ultraviolet light and
gamma irradiation. Thiamine reacts strongly in Maillard-type
reactions.
Thiamine, sometimes called aneurin, is a water-soluble vitamin
of the B complex (vitamin B1), whose phosphate derivatives are
involved in many cellular processes. The best characterized form is
thiamine diphosphate (ThDP), a coenzyme in the catabolism of
sugars and amino acids. In yeast, ThDP is also required in the first
step of alcoholic fermentation.
Thiamine is synthesized in bacteria, fungi and plants. Animals
must cover all their needs from their food and insufficient intake
results in a disease called beriberi affecting the peripheral nervous
system (polyneuritis) and/or the cardiovascular system, with fatal
outcome if not cured by thiamine administration. In less severe
deficiency, nonspecific signs include malaise, weight loss, irritability
and confusion. Today, there is still a lot of work devoted to
elucidating the exact mechanisms by which thiamine deficiency
leads to the specific symptoms observed (see below). Finally, new
thiamine phosphate derivatives have recently been discovered,
emphasizing the complexity of thiamine metabolism and the need
for more research in the field.
Pyridoxine
Pyridoxine is one of the compounds that can be called
vitamin B6, along with pyridoxal and pyridoxamine. It differs from
pyridoxamine by the substituent at the '4' position. It is often used as
'pyridoxine hydrochloride. Pyridoxine assists in the balancing of
sodium and potassium as well as promoting red blood cell
production. It is linked to cardiovascular health by decreasing the
formation of homocysteine. It has been suggested that Pyridoxine
might help children with learning difficulties, and may also prevent
dandruff, eczema, and psoriasis. In addition, pyridoxine can help
balance hormonal changes in women and aid in immune system.
Lack of pyridoxine may cause anemia, nerve damage,
seizures, skin problems, and sores in the mouth. It is
required for the production of the monoamine
neurotransmitters serotonin, dopamine, norepinephrine and
epinephrine, as it is the precursor to pyridoxal phosphate:
cofactor for the enzyme aromatic amino acid
decarboxylase. This enzyme is responsible for converting
the precursors 5-hydroxytryptophan (5-HTP) into serotonin
and levodopa (L-DOPA) into dopamine, noradrenaline and
adrenaline. As such it has been implicated in the treatment
of depression and anxiety. A very good source of
pyridoxine is dragon fruit from South East Asia
.Pyridoxine is not normally found in plants and plants are
not the principal source of this vitamin. This vitamin is
made by certain bacteria. Some vegetarians may get
adequate pyridoxine simply from eating plants that have
traces of soil (like potato skins). Most people get their
supply of this vitamin from either milk or meat products.
Niacin
Niacin, also known as vitamin B3 or nicotinic acid, is a watersoluble vitamin that prevents the deficiency disease pellagra. It is an
organic compound with the molecular formula C6H5NO2. It is a
derivative of pyridine, with a carboxyl group (COOH) at the 3position. Other forms of vitamin B3 include the corresponding
amide, nicotinamide ("niacinamide"), where the carboxyl group has
been replaced by a carboxamide group (CONH2), as well as more
complex amides and a variety of esters. The terms niacin,
nicotinamide, and vitamin B3 are often used interchangeably to
refer to any one of this family of molecules, since they have a
common biochemical activity.
Niacin is converted to nicotinamide and then to NAD
and NADP in vivo. Although the two are identical in their
vitamin activity, nicotinamide does not have the same
pharmacological effects as niacin, which occur as sideeffects of niacin's conversion. Thus nicotinamide does not
reduce cholesterol or cause flushing, although
nicotinamide may be toxic to the liver at doses exceeding 3
g/day for adults. Niacin is a precursor to NADH, NAD,
NAD+, NADP and NADPH, which play essential
metabolic roles in living cells. Niacin is involved in both
DNA repair, and the production of steroid hormones in the
adrenal gland. Niacin is one of five vitamins associated
with a pandemic deficiency disease: these are niacin
(pellagra), vitamin C (scurvy), thiamine (beriberi), vitamin
D (rickets), and vitamin A (vitamin A deficiency, which
has no common name but is one of the most common
symptomatic deficiencies worldwide)
Biotin
Biotin, also known as vitamin H or B7, has the chemical
formula C10H16N2O3S (Biotin; Coenzyme R,
Biopeiderm), is a water-soluble B-complex vitamin
which is composed of an ureido (tetrahydroimidizalone)
ring fused with a tetrahydrothiophene ring. A valeric acid
substituent is attached to one of the carbon atoms of the
tetrahydrothiophene ring. Biotin is a cofactor in the
metabolism of fatty acids and leucine, and in
gluconeogenesis.
Biotin is widely distributed in a variety of foods,
but most often at low concentrations. Estimates are that
the typical U.S. diet provides roughly 40 ug/day. There
are only a couple of foods which contain biotin in large
amounts, including royal jelly and brewer's yeast The
best natural sources of biotin in human nutrition are
liver, legume, soybeans, swiss chard, tomatoes, romaine
lettuce, and carrots. This includes almonds, eggs,
onions, cabbage, cucumber, cauliflower, goat's milk,
cow's milk, raspberries, strawberries, halibut, oats, and
walnuts. The most important natural sources in feeding
nonruminant animals are oilseed meals, alfalfa, and
dried yeasts. It is important to note that the biotin
content of food varies and can be influenced by factors
such as plant variety, season, and yield (endosperm-topericarp ratio).
Riboflavin
Riboflavin (E101), also known as vitamin B2, is an easily
absorbed micronutrient with a key role in maintaining health in
humans and animals. It is the central component of the cofactors
FAD and FMN, and is therefore required by all flavoproteins. As
such, vitamin B2 is required for a wide variety of cellular processes.
Like the other B vitamins, it plays a key role in energy metabolism,
and is required for the metabolism of fats, ketone bodies,
carbohydrates, and proteins. Milk, cheese, leafy green vegetables,
liver, kidneys, legumes such as mature soybeans, yeast, and
almonds are good sources of vitamin B2, but exposure to light
destroys riboflavin. The name "riboflavin" comes from "ribose"
and "flavin".
Vitamin B12 is a water soluble vitamin with a key role in the normal
functioning of the brain and nervous system, and for the formation of
blood. It is one of the eight B vitamins. It is normally involved in the
metabolism of every cell of the body, especially affecting DNA synthesis
and regulation, but also fatty acid synthesis and energy production. Vitamin
B12 is the name for a class of chemically-related compounds, all of which
have vitamin activity. It is structurally the most complicated vitamin.
Biosynthesis of the basic structure of the vitamin can only be accomplished
by bacteria, but conversion between different forms of the vitamin can be
accomplished in the human body. A common synthetic form of the vitamin,
cyanocobalamin, does not occur in nature, but is used in many
pharmaceuticals, supplements and as food additive, due to its stability and
lower cost.
In the body it is converted to the physiological forms, methylcobalamin and
adenosylcobalamin, leaving behind the cyanide, albeit in minimal concentration.
More recently, hydroxocobalamin, methylcobalamin and, adenosylcobalamin can
also be found in more expensive pharmacological products and food supplements.
The utility of these is presently debated.
Historically, vitamin B12 was discovered from its relationship to the disease
pernicious anemia, which is an autoimmune disease that destroys parietal cells in
the stomach that secrete intrinsic factor. Intrinsic factor is crucial for the normal
absorption of B12, therefore, a lack of intrinsic factor, as seen in pernicious anemia,
causes a vitamin B12 deficiency. Many other subtler kinds of vitamin B12
deficiency, and their biochemical effects, have since been elucidated. Vitamin B12
is normally involved in the metabolism of every cell of the body, especially
affecting the DNA synthesis and regulation but also fatty acid synthesis and energy
production. However, many (though not all) of the effects of functions of B12 can
be replaced by sufficient quantities of folic acid (another B vitamin), since B12 is
used to regenerate folate in the body. Most "B12 deficient symptoms" are actually
folate deficient symptoms, since they include all the effects of pernicious anemia
and megaloblastosis, which are due to poor synthesis of DNA when the body does
not have a proper supply of folic acid for the production of thymine.
The "antiscorbutic" factor of fresh fruits, which prevents the
development of the typical symptoms of scurvy in humans, is a
carbohydrate derivative known as vitamin C or ascorbic acid. This
substance is not a carboxylic acid, but a lactone, and owes its acidic
properties (and ease of oxidation) to the presence of an enediol
grouping. It belongs to the L series by the glyceraldehyde
convention.
Most animals are able to synthesize vitamin C in their livers
but, in the course of evolution, man has lost this capacity.
17.Water insoluble (lipid-soluble) vitamines.
Vitamin K (K from "Koagulations-Vitamin" in
German and Scandinavian languages) denotes a group of
lipophilic, hydrophobic vitamins that are needed for the
posttranslational modification of certain proteins, mostly
required for blood coagulation. Chemically they are 2methyl-1,4-naphthoquinone derivatives. Vitamin K1 is also
known as phylloquinone or phytomenadione. Vitamin K2
(menaquinone, menatetrenone) is normally produced by
bacteria in the intestines, and dietary deficiency is
extremely rare unless the intestines are heavily damaged,
are unable to absorb the molecule, or due to decreased
production by normal flora, as seen in broad spectrum
antibiotic acid. There are three synthetic forms of vitamin
K, vitamins K3, K4 and K5 which are used in many areas
including the pet food industry (vitamin K3) and to inhibit
fungal growth (vitamin K5)
Retinol, the animal form of vitamin A, is a fat-soluble
vitamin important in vision and bone growth. It is also a
diterpenoid. Retinol is among the most useable forms of vitamin
A, which also include Retinal (aldehyde form), Retinoic acid (acid
form) and retinyl ester (ester form). These chemical compounds
are collectively known as Retinoids, and all possess the biological
activity of all-trans retinol as a common feature in their structure.
Structurally, retinoids possess a β-ionone ring and a
polyunsaturated side chain, with either an alcohol, aldehyde, a
carboxylic acid group or an ester group. The side chain is
composed of four isoprenoid units, with a series of conjugated
double bonds which may exist in trans or cis configuration.
Retinol is ingested in a precursor form; animal sources (liver
and eggs) contain retinyl esters, whereas plants (carrots, spinach)
contain pro-vitamin A carotenoids. Hydrolysis of retinyl esters
results in retinol, while pro-vitamin A carotenoids can be cleaved
to produce retinal. Retinal, also known as retinaldehyde, can be
reversibly reduced to produce retinol or it can be irreversibly
oxidized to produce retinoic acid. The best described active
retinoid metabolites are 11-cis-retinal and the all-trans and 9-cisisomers of retinoic acid.
Vitamin D is a group of fat-soluble prohormones, the two major
forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or
cholecalciferol). The term vitamin D also refers to metabolites and other
analogues of these substances. Vitamin D3 is produced in skin exposed to
sunlight, specifically ultraviolet B radiation.
Vitamin D deficiency can result from inadequate
intake coupled with inadequate sunlight exposure,
disorders that limit its absorption, conditions that
impair conversion of vitamin D into active
metabolites, such as liver or kidney disorders, or,
rarely, by a number of hereditary disorders.
Deficiency results in impaired bone mineralization,
and leads to bone softening diseases, rickets in
children and osteomalacia in adults, and possibly
contributes to osteoporosis. However, sunlight
exposure, to avoid deficiency, carries other risks,
including skin cancer; this risk is avoided with dietary
absorption, either through diet or as a dietary
supplement.
Vitamin D plays an important role in the maintenance of
organ systems:
 Vitamin D regulates the calcium and phosphorus levels in
the blood by promoting their absorption from food in the
intestines, and by promoting re-absorption of calcium in
the kidneys, which enables normal mineralization of
bone and prevents hypocalcemic tetany. It is also
needed for bone growth and bone remodeling by
osteoblasts and osteoclasts..
 In the absence of vitamin K or with drugs (particularly
blood thinners) that interfere with Vitamin K metabolism,
Vitamin D can promote soft tissue calcification.
 It inhibits parathyroid hormone secretion from the
parathyroid gland.
 Vitamin D affects the immune system by promoting
phagocytosis, anti-tumor activity, and
immunomodulatory functions.
• Tocopherol (or TCP), a class of chemical compounds of
•
which many have vitamin E activity, describes a series of
organic compounds consisting of various methylated
phenols. Because the vitamin activity was first identified in
1936 from a dietary fertility factor in rats, it was given the
name "tocopherol" from the Greek words “τοκος” [birth],
and “φορειν”, [to bear or carry] meaning in sum "to carry a
pregnancy," with the ending "-ol" signifying its status as a
chemical alcohol.
Tocotrienols, which are related compounds, may also have
vitamin E activity. All of these various derivatives with
vitamin activity may correctly be referred to as "vitamin E."
Tocopherols and tocotrienols are fat-soluble antioxidants
but also seem to have many other functions in the body. The
compound α-tocopherol, a common form of tocopherol
added to food products, is denoted by the E number E307.
Thank you for attention!