Fields of Chemistry
Inorganic
Organic
• All molecules in organic chemistry must contain
carbon – in an organified manner – which
basically says you need some hydrogens- thus
organic chemistry is a “Hydrocarbon” chemistry
• CO2 contains carbon – but since it does not
contain hydrogen – it is inorganic
Biochemistry
Animal
Plant
Human Other Animals
Since our focus is on human biochemistry – we
will discuss the major biochemical molecules
carbohydrates, lipids, proteins and nucleic acids
The Carbohydrates, Lipids, Nucleic
Acids have two main commonalities
(1) a monomer to polymer relationship
(2) Interaction of Water into the chemical
reactions
Organic Chemistry is a covalently bonded
chemistry – thus all the chemical bonds
joining monomers are covalent bonds
Monomer to Polymer Relationship
• A monomer is as individual unit capable of
repeat
• The individual unit is a molecule itself
• The monomers chemically bond together to
form “polymers” – the repeated unit
• Monomer of carbohydrate is termed a
monosaccharide (glucose is an example)
• Monomer
Chemical Bond
•
Polymer
•
Interaction (Insertion) of Water into the
chemical reactions
H HO
• H20 Inserted -- result water molecule splits and
one molecule gets the H and other the OH
• If a molecule of water is introduced into the chemical
bond it will split it apart (hydration decomposition or
hydrolysis decomposition)
Interaction (Removal) of Water into the
chemical reactions
H HO
•
result
H20 removed
• -- result water molecule reformed and chemical
bond reformed between the monomers. This is
called dehydration (remove water) synthesis
(anabolic process)
Carbohydrates
• Carbon, hydrogen, and oxygen are in 1:2:1 ratio.
• Most important as source of energy.
• Monosaccharide – simple sugar. 3-7 carbon atoms.
– Triose – 3 carbons
– Tetrose – 4 carbons
– Pentose – 5 carbons
– Hexose – 6 carbons
– Heptose – 7 carbons
• Glucose is a hexose
Glucose
• May form straight chain or a ring structure.
• Ring is more common in human body.
Carbon – Why for life?
• Carbon has an atomic number of 6 – with 4
electrons in is outer energy level – thus it
needs four more electrons. Carbon can
combine covalently with 4 atoms to give it its
4 electrons. The fact that one carbon atom
can combine with so many atoms – gives it
tremendous diversity – thus the basis of life
on this planet.
x2
•
x 1 C x3
•
x4
Carbon likes to bond to Carbon
Carbon Backbone
• Though carbon can bond to 4 different atoms
– it generally likes to bond to itself forming a
“carbon backbone”
C C C C C C
When I quickly draw a ring structure – the corners
always mean carbon unless I put some other atom
there.
Nomenclature Naming of Organic Compounds
• In an organic chemistry course this subject would be,
in detail, discussed – but it is beyond the scope of
this course.
• Just for example
• How many carbons? Prefix - meth 1 eth 2 prop 3 but
4 pent 5 hex 6
• Do you have double covalent bonds present in the
molecule? Suffix – ane if no double bonds, ene if
double bonds
• C C C
versus C C
C
• Propane
Propene
Isomers
• Molecules with the same molecular formula but a
change in structural formula
• C6H12O6 is the formula for glucose, fructose and
galactose – the atoms are arranged differently in
3 –D space for each of those molecules
• Just like in our large world – shape makes a
difference – so is the case in the molecular world
– the arrangement of atoms in 3 –D space defines
the molecule – switch the atoms around in the
molecule and you form a new molecule
ISOMERS
• The body usually treats different isomers as
distinct (different) molecules.
• Simple sugars such as glucose and fructose are
isomers.
• Fructose is a hexose found in most fruits and
in secretions of the male reproductive tract.
• So, separate enzymes and reaction sequences
control its breakdown and synthesis.
Types of Isomers
• Structural Isomers
• Geometric Isomers (Cis-Trans)
• Optical Isomers
Monosaccharide
• The monomer (individual molecule capable of
repeat) of a carbohydrate is termed a
“Monosaccharide”
• Its empirical formula is CH2O
• The most notable monosaccharides
glyceraldehyde (3-carbon carbohydrate),
ribose and deoxyribose (5-carbon
carbohydrate, glucose, galactose and fructose
(6-carbon carbohydrate)
Bonding Carbohydrate monomers together
• Monosaccharides bond together by the
removal of a water molecule (dehydration
synthesis) to form a covalent bond between
the two monosaccharides known as a
“glycosidic bond”
• When bond two monosaccharides together
termed a disaccharide, when join 3 – 10
together termed an Oligosaccharide – more
than 10 together – termed a polysaccharide
Common Disaccharides
• Sucrose – table sugar (glucose alpha 1,2 to
fructose)
• Maltose – in beer (glucose alpha 1,4 to glucose)
• Lactose – in milk (galactose beta 1, 4 to glucose)
Disaccharides
• Most foods contain disaccharides, but all
carbohydrates except simple sugars must be
broken down by hydrolysis before they can
provide useful energy.
• Most commonly used in junk foods and
candies, sodas.
Oligosaccharides
• Carbohydrates with 3 – 10 monosaccharides bonded
together
• Oligosaccharides are often found as a component of
glycoproteins or glycolipids and as such are often
used as chemical markers, often for cell recognition.
• An example is ABO blood type specificity. A and B
blood types have two different oligosaccharide
glycolipids embedded in the cell membranes of the
red blood cells, AB-type blood has both, while O
blood type has neither.
Polysaccharides
• Carbohydrates consisting of greater than 10
monosaccharides bonded together
• Food wise some are termed the “starches”
and one is termed “fiber”
• Their purposes are either for
(1) Storage of energy (glycogen, amylose,
amylopectin) or
(2) Structure (Cellulose, chitin)
Polysaccharides
•
•
•
•
Can be straight chained or highly branched.
Starches are glucose-based polysaccharides.
Most starches manufactured by plants.
Most starches can be broken down by human
digestive tract.
• Cellulose is a polysaccharide that humans
cannot break down.
• Provide bulk for digestive purposes.
STARCH
Glycogen
• Animal starch
• Branched polysaccharide composed of
interconnected glucose molecules.
• Does not dissolve in water.
• Liver and muscles manufacture and store
glycogen.
Lipids
• Contain carbon, hydrogen, and oxygen, but not in
same ratio as carbohydrates.
• In general, contains much less oxygen.
• May also contain phosphorous, nitrogen, or
sulfur.
• Most lipids are insoluble in water, so there are
special transport mechanisms to carry them in
the blood.
Lipids
• Form structural components of all cells.
• Important as energy reserves.
• Lipids provide twice the energy gram for gram
as carbohydrates.
• Fat: 1 gram = 9 calories
• Carbohydrates: 1 gram = 4 calories
Lipids
• Account for 10 – 12 percent of body weight
(normal or average),
• We will consider 5 types of lipids:
• 1. fatty acids
• 2. eicosanoids
• 3. glycerides
• 4. steroids
• 5. phospholipids and glycolipids
Unsaturated Fat
Solid Fat versus Liquid Fat at Room Temperature
Fatty acids
• Long carbon chains with hydrogens attached.
• One end of the chain ALWAYS has a carboxylic
acid group attached to it.
Typical fatty acids. Note the carboxylic acid end.
Carboxylic acid: CO2H
Fatty acids
• The name carboxyl should help you remember
that a carbon and hydoxyl (-OH) group are in
it.
• The end opposite the carboxylic acid end is
the hydrocarbon “tail”.
• When a fatty acid is placed in solution, only
the hydrophilic carboxyl end associates with
water molecules.
• The rest of the chain is hydrophobic.
Fatty acids
• Saturated – each carbon atom has four single
covalent bonds.
• Unsaturated – Some of the carbon – carbon
bonds are double bonds, thus reducing the
number of hydrogens.
• Monounsaturated – one double bond in the
molecule.
• Polyunsaturated – numerous double bonds in
the molecule.
Fatty acids and Health
• Both saturated and unsaturated fats can be
broken down for energy.
• Large amounts of saturated fats increases risk
of heart disease.
• Current research suggests monounsaturated
fats may be more effective than
polyunsaturated fats in lowering risk of heart
disease.
Fatty acids and Health
• When margarine and vegetable shortening
(CRISCO) are manufactured from
polyunsaturated fats.
• Hydrogen is added to break double bonds to
make the fat more solid (for baking,
palatability, etc.), trans fatty acids are
produced, which increase risk of heart
disease.
Fatty acids and Health
• A carbon in a fatty acid molecule is numbered
beginning at the carboxylic acid end.
• The last carbon in the chain is called the
“omega” carbon.
• So, if you have a double bond three carbons
before the omega carbon, you have an
“Omega-3 fatty acid”
Cis versus Trans Fatty Acids
Eicosanoids
• Lipids derived from arichidonic acid.
• Arachidonic acid cannot be synthesized by the
body, so we have to get it through diet.
• Two major classes of eicosanoids:
– Prostaglandins
– Leukotrienes
Virtually all tissues synthesize and respond to
prostaglandins, so lekotrienes will be talked about
later.
Prostaglandins
• Short chained fatty acids that have 5 of their
carbon atoms arranged in rings.
• Coordinate and direct cell activities.
• Powerful and effective in small quantities.
• Examples: released by damaged tissue to
stimulate pain receptors.
• Start uterine contractions in birthing process.
Prostaglandins
Prostaglandins
• Usually do not travel through circulatory
system to reach target cell.
• So prostaglandins are called local hormones.
Glycerides
• Individual fatty acids cannot be strung
together in a chain like the simple sugars.
• They can be attached to another compound
called glycerol.
• The result is a lipid call a glyceride.
• A dehydration synthesis can produce a
monoglyceride which is glycerol plus one fatty
acid.
Glycerides
• Each additional reaction can produce a
diglyceride (glycerol plus two fatty acids) or a
triglyceride (glycerol plus three fatty acids).
Triglycerides
• Known as neutral fats.
• Have 3 important functions:
Triglyceride function 1
• Fatty deposits in body are energy reserves.
• In times of need, the triglycerides are
disassembled to yield fatty acids that can be
broken down to form energy.
Triglyceride function 2
• Fat deposits under skin serve as insulation.
• Heat loss through a layer of lipids is about
one-third that of other tissues.
Triglyceride function 3
• Fat deposits around organs provide cushioning
and protection.
Triglycerides
• Stored in body as lipid droplets within cells.
• These absorb and accumulate lipid-soluble
drugs, vitamins, or toxins.
• Good and bad: Store vitamins A, D, E and K
• Store pesticides such as DDT.
• Marijuana Is A Fat Soluble Substance
Function of Cholesterol and other Steroids
1. Cholesterol is required to build and maintain cell
membranes.
2. Within the cell membrane, cholesterol also
functions in intracellular transport, cell signalling
and nerve conduction.
3. Cholesterol is an important precursor molecule
for the synthesis of Vitamin D and the steroid
hormones, including the adrenal gland
hormones cortisol and aldosterone as well as
the sex hormones progesterone, estrogens, and
testosterone and their derivatives.
Cholesterol Structure
Cholesterol is a sterol type steroid - are also known as
steroid alcohol. When a steroid has an OH (hydroxyl)
group at the 3-position of the A-ring – it is termed a
sterol.
Cholesterol
Where does cholesterol come
from?
• Obtained from 2 sources:
– Absorption from animal products in diet.
– Synthesis within the body.
There is a strong link between high cholesterol
intake and heart disease.
Sice body makes cholesterol, it is sometimes difficult
to lower cholesterol levels only with diet.
Types of cholesterol
• There are two types of cholesterol: "good"
and "bad." It's important to understand the
difference, and to know the levels of "good"
and "bad" cholesterol in your blood. Too much
of one type — or not enough of another —
can put you at risk for coronary heart disease,
heart attack or stroke.
Types of cholesterol
• HDL is the "good" cholesterol which helps
keep the LDL (bad) cholesterol from getting
lodged into your artery walls. A healthy level
of HDL may also protect against heart attack
and stroke, while low levels of HDL (less than
40 mg/dL for men and less than 50 mg/dL for
women) have been shown to increase the risk
of heart disease.
Types of cholesterol
• The 4-ring region of cholesterol is the
signature of all steroid hormones (such as
testosterone and estrogen). All steroids are
made from cholesterol.
• The combination of the steroid ring structure
and the hydroxyl (alcohol) group classifies
cholesterol as a "sterol." Cholesterol is the
animal sterol. Plants only make trace amounts
of cholesterol, but make other sterols in larger
amounts.
Types of cholesterol
• Because cholesterol contains both a watersoluble region and a fat-soluble region, it is
called amphipathic.
• Cholesterol, however, is not water-soluble
enough to dissolve in the blood. Along with
fats and fat-soluble nutrients, therefore, it
travels in the blood through lipoproteins such
as LDL and HDL.
Types of cholesterol
• HDL and LDL stand for "high-density
lipoprotein" and "low-density lipoprotein."
VLDL stands for "very low-density
lipoprotein," IDL stands for "intermediatedensity lipoprotein" and Lp(a) stands for
"lipoprotein (a)."
LDL
• LDL that does not get taken up into cells tends
to oxidize. The polyunsaturated fatty acids
(PUFA) in its membrane get damaged by free
radicals, and then they proceed to damage the
protein in the surface, and finally the fatty
acids and cholesterol in the core.
• Once LDL oxidizes, it can invade the arterial
wall in areas that experience disturbed blood
flow, like the points were arteries curve or
branch.
LDL
• These areas, especially in people who do not
exercise enough, are permeable to large
molecules. Oxidized lipids cause them to
attract white blood cells and initiate an
inflammatory cascade that produces arterial
plaque.
HDL
• HDL particles can extract free cholesterol from
cell membranes and attach it to fatty acids,
producing cholesterol esters. They generally
pass this off to LDL and other apoB-containing
proteins in exchange for fats, also called
triglycerides, and fat-soluble vitamins such as
vitamin E. The result is that, over time, HDL
tends to be rich in fats and vitamin E, while
the other lipoproteins, especially LDL, are rich
in cholesterol.
HDL
• HDL delivers vitamin E to the endothelial cells
that line the blood vessel wall.
• Both HDL and isolated Vitamin E suppress the
ability of these cells to oxidize LDL with free
radical-generating enzymes and also suppress
their production of inflammatory molecules
that attract the white blood cells that invade
the arterial wall to form arterial plaques.
Steroids
• Large lipid molecules that share a common,
distinctive carbon framework.
Steroid functions
• Regulation of sexual function. Testosterone
and Estrogen.
• Regulation of tissue metabolism and mineral
balance. Adrenal cortex hormones
corticosteroids and calcitrol.
• Derivatives called bile salts required for
normal processing and breakdown of dietary
fats. Produced in liver and store/secreted by
gall bladder.
Phospholipids and glycolipids
• Structurally related.
• Body can produce both of them.
• Phospholipid – phosphate group links a
diglyceride to a nonlipid group.
• Glycolipid – carbohydrate is linked to a
glyceride.
GLYCOLIPID
Protein
• A Protein is a polymer made up of monomers
termed “amino acids”
Protein functions
1. Support: structural proteins create a threedimensional framework for the body and
cells.
2. Movement: contractile proteins responsible
for muscle contraction. Related proteins
responsible for movement of individual cells.
3. Transport: lipids, respiratory gases, minerals,
and hormones are bound to transport
proteins.
Protein functions
4. Buffering: prevent dangerous changes in pH.
5. Metabolic regulation: Enzymes accelerate
chemical reactions in living cells. Enzymes
are very sensitive to environmental
conditions such as pH and temperature.
Control pace and direction of metabolic
pathways.
6. Coordination and control: Influence
metabolic activities of every cell in body. Can
affect a specific function of specific organs or
organ systems.
7. Defense: Waterproof proteins of skin, hair,
and nails.
•
•
Antibodies- protect from disease
Clotting proteins – restrict bleeding
Proteins are made-up of monomers called “amino
acids. There 20 naturally occurring amino acids.
Structure of proteins
•
•
•
•
Long chains of amino acids.
Typical protein has about 1000 amino acids.
Largest proteins may have 100,000 or more.
Each amino acid composed of a central carbon
atom to which four groups are attached:
– Hydrogen atom
– Amino group (-NH2)
– Carboxylic acid group (-COOH)
– Variable group known as R or side chain.
Structure of proteins
• Different R groups distinguish one amino acid
from another, giving each its unique chemical
properties.
• The name amino acid refers to the presence of
the amino group and the carboxylic acid
group.
• AAs are relatively small, water soluble
molecules.
POLYPEPTIDES
Amino acids join together by performing
dehydration synthesis
Figure 2.17
Peptide bonds
• Two amino acids can be linked together by
dehydration synthesis.
• This creates a covalent bond between the
carboxylic acid group of one amino acid and
the amino group of another.
• This bond is known as a peptide bond.
• Two amino acids joined together would be a
dipeptide.
Peptides
•
•
•
•
2 AA = dipeptide
3 AA = tripeptide
Tripeptides and larger are called polypeptides
If have more than 100 AA, it is called a
protein.
Charge of a protein
• At pH of body, carboxylic acid groups of AA
give up their hydrogens.
• When the carboxylic acid group changes from
–COOH to –COO- , they become negatively
charged.
• So an entire protein always has a negative
charge and is sometimes abbreviated as Pr-
R group still free
Structure of proteins
• The primary structure of proteins:
– the order of the amino acids joined together to
make the protein.
– Using three letter abbreviations, a bit of a protein
chain might be represented by, for example:
• gly-gly-ser-ala is the primary structure for a polypeptide
composed of , glycine, glycine, serine, and alanine, in that
order, from the N-terminal amino acid (glycine) to the Cterminal amino acid (alanine).
Structure of proteins
• The secondary structure of proteins:
• Within the long protein chains there are regions in
which the chains are organized into regular
structures known as alpha-helices (alpha-helixes) and
beta-pleated sheets. These are the secondary
structures in proteins.
• These secondary structures are held together by
hydrogen bonds. These form as shown in the
diagram between one of the lone pairs on an oxygen
atom and the hydrogen attached to a nitrogen atom:
Structure of proteins
• The tertiary structure of proteins
– The tertiary structure of a protein is a description
of the way the whole chain (including the
secondary structures) folds itself into its final 3dimensional shape.
– The tertiary structure of a protein is held together
by interactions between the the side chains - the
"R" groups.
Structure of proteins
• Quaternary Structure:
– refers to the regular association of two or more
polypeptide chains to form a complex.
– Multimeric proteins contain two or more
polypeptide chains, or subunits, held together by
noncovalent bonds. Quaternary structure
describes the number (stoichiometry) and relative
positions of the subunits in a multimeric protein.
– There are two major categories of proteins with
quaternary structure - fibrous and globular.
Fibrous Proteins:
• fibrous proteins such as the keratins in wool
and hair are composed of coiled alpha helical
protein chains with other various coils
analogous to those found in a rope.
Globular Proteins:
• globular proteins may have a combination of
the above types of structures and are mostly
clumped into a shape of a ball. Major
examples include insulin, hemoglobin, and
most enzymes.
Primary Structure – linear sequence of Amino
Acids (the only thing DNA codes for directly)
Secondary Structure – does the Polypeptide or protein
have repeating regions (alpha helix or beta pleated
sheet). Secondary structuring is held together by
hydrogen bonds
Tertiary Structure – describe the 3-D fold of the
single stranded Polypeptide or Protein (held together
by different types of chemical bonds depending on
location and AA
Quaternary structure – if the protein is made-up of
more than one polypeptide chain (strand) – the
quaternary structure is the shape of the entire protein
(inclusive of all its strands)
Fibrous Protein (L) Globular Protein (R)
Shape and Function
• The shape of a protein determines its
functional properties.
• Then shape is determined by the sequence of
the amino acids.
• If one amino acid is changed in a protein
consisting of 10,000 or more AA , the shape
and function are altered.
Shape and Function
• Several cancers and sickle cell anemia are the
result of a sigle change in the AA sequence of
a protein.
• Tertiary and quaternary structures depend on
the amino acid sequence and also the local
environment characteristics.
• If temperature or pH of the surroundings
change, it can affect the function of a protein.
Shape and Function
• Protein shape can also be affected by
hydrogen bonding to other molecules in
solution.
• This is significant especially when considering
the functions of the proteins called enzymes.
Enzymes
(a Biologic catalyst)
• A catalyst is a chemical additive that accelerates a
chemical reaction without itself being consumed
in the reaction.
• By the catalyst not being consumed in the
chemical reaction – it is capable on working overand-over again on several reactions of the same
kind
• An enzyme is a biologic catalyst- thus it is a
biochemical additive that accelerates a
biochemical reaction without itself being
consumed in the reaction
What does an enzyme do to the energy of
activation?
• It lowers the energy of activation
• Key issue: An enzyme lowers the energy of
reaction – but it in no way donates any energy to
the reaction.
• If an enzyme donated energy to a reaction – it
would slowly but surely become consumed in
the reaction - REMEMBER THE DEFINITION
An enzyme lowers the
energy of activation
Figure 2.20
How does an enzyme lower the energy of
activation?
• Before an enzyme can function as a catalyst,
the substrates in the reaction must bind to a
specific region of the enzyme called the active
site.
• The tertiary or quaternary structure
determines the shape of the active site,
typically a groove or pocket where the
substrates can nestle.
• There are two active site shape models –
– Lock and Key
– Induced Fit
Lock and Key model
Lock and Key model
• In this model, the amino acids that make up
an enzyme's active site in the unbound state
are said to form a shape that exactly matches
the shape of the substrate. Thus, the substrate
fits into this active site, just as a key fits into a
lock whose shape is designed to match the
key.
Lock and Key
• However, the active sites of many enzymes do
not have a shape in the unbound form that
exactly matches the shape of the substrate.
The shape of the active site changes when the
substrate binds to the enzyme, creating a
shape into which the substrate fits.
• This is known as induced fit model.
Induced fit model
All enzymes share three basic
characteristics
• 1. Specificity – each enzyme catalyzes only
one type of reaction and can accommodate
only one type of substrate molecule.
• 2. Saturation limits – the rate of reaction is
directly proportional to the concentration of
substrate and enzymes. When substrate
molecules are high enough in concentration
that all enzymes are being used, further
increases in substrate concentration will not
increase the reaction rate.
Enzyme characteristics
• Saturation limit cont. – the substrate
concentration required for the maximum
reaction rate is called the saturation limit.
• An enzyme reaching the saturation limit is
saturated.
Enzyme characteristics
• Regulation – a variety of factors can turn
enzymes off or on in a cell in order to control
reaction rates.
• One example is the presence of cofactors.
• Every cell has lots of enzymes, so inactivation
and activation of these enzymes is important
for control of cellular activities.
• The activation/deactivation is immediate.
Cofactors
• Ions or molecules that must bind to the
enzyme before the enzyme can bind the
substrate.
• Calcium, magnesium are examples
Coenzymes
• Non-protein organic molecules.
• Vitamins are common cofactors.
Apoenzymes and Holoenzymes
• Apoenzyme- An enzyme that requires a
cofactor but does not have one bound. An
apoenzyme is an inactive enzyme, activation
of the enzyme occurs upon binding of an
organic or inorganic cofactor.
• Holoenzyme- An apoenzyme together with its
cofactor. A holoenzyme is complete and
catalytically active.
The Imposters
What are the inhibitors?
• Enzyme inhibitors are molecules that bind to
enzymes and decrease their activity (slow down the
reaction).
• The imposter (inhibitor) molecule has a shape
similar to the real substrate - remember in the
induced fit model -the active site does not exactly
fit the substrates – like in the old Lock and Key
model – thus look-alike imposters could enter the
active site
• Enzyme inhibitors can be bad – like taking a
poison
• Enzyme inhibitors can be good – for example
some of the antibiotics – they block a vitally
needed enzyme in the pathogen’s
biochemistry – but we don’t have the same
enzyme -so it kills the pathogen but does not
bother us.
Types of Inhibitors
Competitive (attached to the active site)
• Reversible (transiently attaches to AS)
• Non-reversible (permanently attaches to AS)
Non-competitive (Attaches to other sites on
the enzyme)
Competitive Inhibition
Non-reversible (Irreversible) Inhibition
Note how the irreversible inhibitor locks on
by strong covalent bonding.
Non-competitive Inhibition
Substrate
Allosteric site where
Non-competitive
Inhibitor binds
Active Site
Enzyme Involvement in Disease
Virtually every chemical step of metabolism is catalyzed by an enzyme.
Disorders of these enzymes that result from abnormalities in their genes are
known as inborn errors of metabolism.
Phenylketonuria (PKU) is the most common disorder of amino acid metabolism,
and it is a paradigm for effective newborn screening. Phenylalanine is an
essential amino acid (meaning that it cannot be synthesized but must be taken
in through the diet). The first step to its breakdown is the phenylalanine
hydroxylase reaction, which converts phenylalanine to another amino acid,
tyrosine. A genetic defect in the phenylalanine hydroxylase enzyme is the basis
for classical PKU. Untreated PKU results in severe mental retardation, but PKU
can be detected by screening newborn blood spots, and the classical form can
be very effectively treated by using medical formulas that are limited in their
phenylalanine content.
Enzymes and disease
• Alkaptonuria is a disorder of tyrosine
breakdown. The intermediate that
accumulates, called homogentisic acid, can
polymerize to form pigment that binds to
cartilage and causes progressive arthritis and
bone disease and that also is excreted to
darken the urine.
Enzymes and disease
• Tay-Sachs disease is due to a defect in the
beta-hexosaminidase A enzyme, which
removes a sugar from certain lipids called
gangliosides, which build up in the lysosome.
The disease causes neurological symptoms, an
enlarged head, and death in early childhood.
Enzyme denaturation
• Every enzyme works best at a narrow pH and
temp. range.
• If temp. increases, proteins change shape and
function deteriorates.
• Body temp. above 110 degrees F causes death
because proteins denature (permanent
change in tertiary or quaternary structure).
• Denatured proteins are non-functional.
Enzyme denaturation
• Enzymes also sensitive to pH changes:
– Pepsin breaks down proteins in stomach and
works at pH of 2.0
– Trypsin also breaks down proteins in small
intestine but works at pH of 7.7
The Nucleic Acids (DNA and RNA)
• DNA is a polymer and is our genetic material
• RNA is a polymer and assists our genetic
material
Nucleic acids
• Large organic molecules composed of carbon,
hydrogen, oxygen, nitrogen, and phosphorous.
• DNA = deoxyribonucleic acid
• RNA = ribonucleic acid
DNA
• Determines inherited characteristics
• Encodes information to make all proteins
needed by body
RNA
• Cooperate to make proteins using information
from DNA.
Structure of nucleic acids
• Nucleic acid is series of nucleotides linked
through dehydration synthesis.
• Nucleotide has three basic components
– Sugar (ribose or deoxyribose)
– Phosphate group
– Nitrogenous base (adenine, guanine, cytosisne,
thymine, uracil)
Fig. 5-27c-1
Each nucleotide
contains one of
these 5 NBs!
Nitrogenous bases
Pyrimidines
Cytosine (C) Thymine (T, in DNA)
DNA has
cytosine ,
adenine,
guanine
and thymine
(DNA has no
uracil)
Uracil (U, in RNA)
RNA has cytosine , adenine, guanine
Purines and uracil (RNA has no thymine)
Adenine (A)
Guanine (G)
(c) Nucleoside components: nitrogenous bases
Fig. 5-27c-2
A nucleotide has one of these two sugars – in DNA the nucleotide
contains Deoxyribose as the sugar ( thus Deoxyribonucleic acid )
and in RNA the nucleotide contains ribose
(thus Ribonucleic Acid)
Sugars
Deoxyribose (in DNA)
Ribose (in RNA)
(c) Nucleoside components: sugars
Ribose has a oxygen at the second carbon and
Deoxyribose does not – thus deoxy
Fig. 5-27
5 end
Nitrogenous bases
Pyrimidines
5C
3C
Nucleoside
Nitrogenous
base
Cytosine (C)
Thymine (T, in DNA) Uracil (U, in RNA)
Purines
Phosphate
group
5C
Sugar
(pentose)
Adenine (A)
Guanine (G)
(b) Nucleotide
3C
Sugars
3 end
(a) Polynucleotide, or nucleic acid
The third component of the nucleotide is
the phosphate group
Deoxyribose (in DNA)
Ribose (in RNA)
(c) Nucleoside components: sugars
Nucleic Acid Structure
• Adenine and Guanine are double ring
structures and called purines.
• Others are single ring and called pyrimidines.
• Uracil found only in RNA, thymine only in
DNA.
• Easy to remember that uracil “replaces”
thymine in RNA.
Nucleic Acid Structure
• The nucleic acids are very large molecules that
have two main parts. The backbone of a
nucleic acid is made of alternating sugar and
phosphate molecules bonded together.
• When a nitrogenous base attaches to a
pentose (ribose or deoxyribose) sugar, a
nucleoside is formed. Nucleoside is named
after the nitrogenous base.
Nucleotide
• When a nucleoside combines with a
phosphate group.
• To make a nucleic acid, dehydration synthesis
attaches the phosphate group of one
nucleotide to the sugar of another.
• The “backbone” of a nucleic acid is a linear
sugar to phosphate to sugar sequence with
the nitrogenous bases projecting to one side.
Single Strand Design of Nucleic Acid
Design
Nitrogenous Base
Sugar
Phosphate group
Nitrogenous Base
Fig. 5-27ab
5' end
5'C
3'C
Nucleoside
Nitrogenous
base
5'C
Phosphate
group
5'C
3'C
(b) Nucleotide
3' end
(a) Polynucleotide, or nucleic acid
3'C
Sugar
(pentose)
DNA Special Bonding of Nitrogenous Bases
• The DNA code (Chargaff’s rule) a purine on
one side hydrogen bonds to a pyrimidine on
the other side
• More specifically if Adenine is on one side it
will hydrogen bond to Thymine on the other
side
• If Cytosine is on one side it will hydrogen bond
to Guanine on the other side - so
A
T
G
C
Figure 2.22a, b
Figure 2.22a
RNA
• Single strand of nucleotides
• Three types:
– Messenger (mRNA)
– Transfer (tRNA)
– Ribosomal (rRNA)
• Each has different shape and function, but all
3 required for protein synthesis.
DNA
• Double strand of nucleotide chains.
• Complementary base pairing:
– Purine bonds with opposing pyrimidine
– Adenine:Thymine
– Guanine:Cytosine
DNA
• The two strands of DNA are anti-parallel
• If one strand is in the 3’
5’ direction – the
other side is in the 5’ 3’ direction
High energy compounds
• Energy in cells obtained from enzymatic
catabolism of organic substrates.
• The energy somehow has to be “captured” so
it can be transferred from one molecule to
another or from one part of the cell to
another.
• Usual method of transfer involves creation of
high-energy bonds.
High energy compounds
• High-energy bond – covalent bond. When
broken down releases energy that can be used
by the cell.
• Humans: phosphate group connected to an
organic molecule.
High energy compounds
• Phosphorylation – attachment of phosphate
group to another molecule.
• High-energy compound requires:
– Phosphate group
– Appropriate enzymes
– Suitable organic substrates
High energy compounds
• Most important substrate is adenosine.
• Adenosine monophosphate (AMP) is
phosphorylated to Adenosine diphosphate
(ADP). This requires significant energy
expenditure.
• Adenosine diphosphate (ADP) is then
phosphorylate to Adenosine triphosphate
(ATP). More energy required at this stage
also.
Energy conversion in cells
• ADP converted to ATP and then reverted to
ADP.
– ADP + phosphate group + energy ↔ ATP + H2O
• Human cells are constantly using this energy
for metabolism, protein synthesis, and
contraction of muscles.
• ATP is most abundant energy source in body.
Other energy sources
• Guanosine triphosphate (GTP)
• Uridine triphosphate (UTP)
• Used in specific enzyme reactions.
Quiz
• 1. Carbohydrates, lipids, and proteins are
formed from their basic building blocks by the:
• A. removal of a water molecule between the
building blocks
• B. addition of a water molecule between the
building blocks
• C. addition of carbon to each molecule
• D. addition of oxygen to each molecule
2.
•
•
•
•
•
Complementary base pairing in DNA includes
A. adenine-uracil; cytosine-guanine
B. adenine-thymine; cytosine-guanine
C. adenine-guanine; cytosine-thymine
D. guanine-uracil; cytosine-thymine
3
• What is the role of enzymes in chemical
reactions?
4
• List three important functions of triglycerides
in the human body.
5
• List seven major functions performed by
proteins.
Review
• P. 67: 21 – 31
• P. 68: 6 and 7
• When finished, continue with tissue and cell
slides. Look at them many times so you can
recognize the different cell and tissue types.