16.1 Intro to Proteins
Proteins are polymers in which the monomer
units are amino acids.
The name “protein” comes from the Greek,
and means “of first importance.”
Proteins are the most abundant biomolecules
in animals (including humans) and have
the widest variety of structures.
Proteins contain nitrogen; carbohydrates and
lipids generally do not.
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3–1
16.2 Amino Acids
An amino acid contains both an amino group
(–NH2) and a carboxylic acid (–COOH).
Both groups are on the same carbon, the
-carbon. The carbon also carries an R
group and a hydrogen atom.
O
H
N
H
C
H
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C
H
O
R
3–2
16.2 Amino Acids
There are 20 standard amino acids, each
with a different R group. There are four
categories of amino acids.
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3–3
16.2 Amino Acids
Polar neutral amino acids.
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3–4
16.2 Amino Acids
Polar
acidic
and
basic
amino
acids.
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3–5
16.2 Amino Acids
Polar
acidic
and
basic
amino
acids.
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3–6
16.2 Amino Acids
Ten amino acids cannot be produced by the
body, and must be obtained through the diet.
These are the essential amino acids.
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3–7
16.3 Handedness
The -carbon in an amino acid is chiral. Most
amino acids have the L-configuration.
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16.4 Acid-Base Properties
Amino acids undergo intramolecular proton
transfer. They always exist as zwitterions
(double, or hybrid) ions.
O
H
N
H
C
C
H
H
H
O
R
Neutral Molecule
O
H N
C
C
O
H
H R
Zwitterion
Zwitterions have no net electrical charge.
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3–9
16.4 Acid-Base Properties
In acidic solution, the carboxylate group
is protonated. This produces a cation.
H
O
H N
C
+ H3O
C
O
H
H R
Zwitterion + acid
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H
O
H N
C
+ H2O
C
OH
H
H R
Positive net charge
3–10
16.4 Acid-Base Properties
In basic solution, the ammonium group is
deprotonated. This produces an anion.
H
O
H N
C
+ OH
C
O
H
H R
Zwitterion + base
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O
H N
C
+ H2O
C
O
H
H R
Negative net charge
3–11
16.4 Acid-Base Properties
The pH at which an amino acid exists as
its uncharged zwitterion is called the
isoelectric point. Neutral amino acids
have isoelectric points about pH 6.
Acidic amino acids have low isoelectric
points, because the carboxylate group
must be protonated.
Basic amino acids have high isoelectric
points, because the amino group must
be deprotonated.
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3–12
16.5 Peptide Formation
Amino acids condense to form amide, or
peptide, bonds. The reactions are catalyzed by enzymes.
H
H
H
N
C
H
R1
H
O
+
C
H
O
H
H
H
N
C
H
R1
a dipeptide
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H
O
N
C
H
R2
enzyme
C
O
O
H
C
N
C
H
R2
O
C
+
H2O
O
3–13
16.5 Peptide Formation
A chain of any length can form.
A polypeptide contains 50 or fewer amino
acid residues.
A protein contains more than 50 amino acid
residues.
Central Dogma of Molecular Biology
Protein synthesis is directed by RNA (ribonunucleic acid). DNA (deoxyribonucleic acid)
acts as a template for RNA synthesis.
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3–14
16.6 - 16.10 Protein Structure
The structure of proteins and peptides is
critical to their function in organisms. It
is divided into four
levels.
Primary structure of
proteins refers to the
sequence of amino
acid residues.
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16.6 - 16.10 Protein Structure
The structure of proteins and peptides is
critical to their function in organisms. It
is divided into four
levels.
Primary structure of
proteins refers to the
sequence of amino
acid residues. The
illustration shows human myobglobin.
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3–16
16.6 - 16.10 Protein Structure
Secondary structure of proteins refers to the
arrangement adopted by the backbone portion of the protein. It results from hydrogen
bonding between N–H and C=O groups.
Two major secondary structures are seen:
the -helix, formed by a coiled chain
the -pleated sheet, formed by hydrogen bonds between extended chains
or segments of a single chain
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16.6 - 16.10 Protein Structure
Views of the -helix, formed by a coiled chain
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16.6 - 16.10 Protein Structure
Views of the -pleated sheet,
formed by hydro-gen bonds
between extended chains or
seg-ments of a single chain
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3–19
16.6 - 16.10 Protein Structure
Views of the -pleated sheet,
formed by hydro-gen bonds
between extended chains or
seg-ments of a single chain
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3–20
16.6 - 16.10 Protein Structure
Tertiary structure refers to the overall
three-dimensional
shape of a protein.
This illustration
shows the structure of myoglobin.
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16.6 - 16.10 Protein Structure
Four types of attractive forces give rise to the
tertiary structure of proteins.
Disulfide bonds
Electrostatic interactions, a.k.a. salt bridges
Hydrogen bonds
Hydrophobic interactions
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16.6 - 16.10 Protein Structure
Disulfide bonds form between –SH groups of
cysteine residues. They are covalent bonds.
C
O
H
C
CH2 SH + HS
H
N
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O
C
CH2 C
H
N
H
C
O
H
C
CH2 S
H
N
enzyme
O
S
C
CH2 C
H
N
H
3–23
16.6 - 16.10 Protein Structure
Disulfide bonds between the two
chains of human insulin.
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16.6 - 16.10 Protein Structure
Electrostatic interactions
between side-chain
carboxylate and ammonium ions are ionic
bonds. They are also
called salt bridges.
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3–25
16.6 - 16.10 Protein Structure
Hydrogen bonds form
between hydroxyl and
amide functional groups
on side chains of amino
acid residues.
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3–26
16.6 - 16.10 Protein Structure
Hydrophobic interactions
occur between nonpolar
side chains on amino
acid residues. They
involve dispersion forces
similar to those that form
micelles.
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16.6 - 16.10 Protein Structure
Quaternary structure refers to the arrangement
of polypeptide chains within a protein that are
not covalently bound to each other.
The chains are bound by the same forces that
give rise to tertiary structure.
The next slide shows the quaternary structure
of hemoglobin.
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3–28
16.6 - 16.10 Protein Structure
Quaternary structure
refers to the
arrangement of
polypeptide chains
within a protein that
are not covalently
bound to each other.
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3–29
16.11 Protein Classification
Proteins can be classified by composition or
by morphology (shape/structure).
Classifications based on composition:
Simple proteins contain only amino acid
residues. More than one chain may be
present.
Conjugated proteins have prosthetic groups,
components that are not made up of amino
acids. These can be organic or inorganic.
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16.11 Protein Classification
Types of conjugated proteins:
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16.11 Protein Classification
Classifications based on morphology:
Fibrous proteins are rod-shaped or stringlike.
They have structural or movement functions.
They have very long chains.
They are not water-soluble.
Globular proteins are “globby.”
They have functions other than structure or
movement.
They have chains of moderate length.
They dissolve in water or form colloids.
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16.11 Protein Classification
Types of fibrous and globular proteins:
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16.11 Protein Functions
1. Catalysis: Proteins called enzymes catalyze
biochemical reactions.
2. Structure: Proteins are the main structural
molecules in animals.
Collagen is found in skin, bone,
connective tissue (tendons, etc.)
Keratin in hair, nails, skin
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16.11 Protein Functions
3. Storage:
Proteins provide a way to store
small molecules or ions in the
organism.
Ovalbumin stores amino acids
in bird eggs.
Casein stores amino acids in
milk.
Ferritin stores iron ions in
animal spleens.
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16.11 Protein Functions
4. Protection: Antibodies form complexes with
foreign protein from viruses and
bacteria, and help destroy them.
Fibrinogen and thrombin are
proteins involved in blood clot
formation.
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16.11 Protein Functions
5. Regulation: Hormones trigger a specific
process in target tissues. Many
are proteins or peptides.
Insulin regulates glucose
metabolism.
Vasopressin regulates volume
of urine and blood pressure.
Oxytocin regulates contraction
of the uterus and lactating
mammary glands.
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16.11 Protein Functions
6. Nerve Impulse Transmission:
Some proteins act as receptors
of small molecules that pass
across synapses, gaps between
nerve cells.
Rhodopsin is a protein in the
retina. It is activated by isomerization of retinal, a molecule
derived from Vitamin A.
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16.11 Protein Functions
7. Movement: Proteins in muscle are responsible for contraction and relaxation.
Actin and myosin are fibrous
proteins that slide across each
other in muscle movement.
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3–39
16.11 Protein Functions
8. Transport: Proteins transport ions and molecules through the blood stream
and other body fluids.
Hemoglobin transports oxygen
through the blood stream.
Serum albumin transports fatty
acids through the blood stream.
Lipoproteins transport lipids
through various body fluids.
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3–40
16.12 Protein Deactivation
Proteins can be deactivated by two processes,
hydrolysis and denaturation.
Hydrolysis is the reverse of peptide bond formation. It reduces a protein to smaller polypeptide molecules and free amino acids.
Hydrolysis can be caused by enzymes or
strong acids or bases. It is part of the normal digestion of proteins in the stomach.
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16.12 Protein Deactivation
Hydrolysis of a tripeptide to amino acids:
H
H
H
H
N
C
H
R1
H
H
N
C
H
R1
O
H
C
N
C
H
R2
O
O
+
C
H
C
H
O
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N
C
H
R3
H
H
N
C
H
R2
H2O
acid, base,
or enzyme
O
C
O
O
+
C
O
H
H
H
N
C
H
R3
O
C
O
3–42
16.12 Protein Deactivation
Denaturation is the partial or complete
disorganization of a protein’s threedimensional shape.
Denaturation is caused by disruption of
the attractive forces that produce this
shape. Heat, acids or bases, detergents, organic solvents, ions of heavy
metals, and violent whipping or
shaking can denature proteins.
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3–43
16.12 Protein Deactivation
Denaturation of a protein:
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16.13 Enzymes
Enzymes are catalysts for biochemical
reactions. Most are globular proteins,
although a few are ribonucleic acids.
Catalysts increase the rate of a chemical
reaction, but they are not consumed in
the reaction.
Enzymes can increase the rate of a reaction by a factor of 10 20 compared to
that of the uncatalyzed reaction.
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16.13 Introduction to Enzymes
Enzyme catalysis has three key characteristics:
Efficiency Reactions are very fast under
mild conditions.
Specificity Enzymes catalyze reactions of
just one compound, or a few
similar compounds (substrates).
Regulation Catalysis can be controlled by
the cells in which reactions
occur.
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16.14 Names and Classification
The name of a specific enzyme has three parts
and ends in “-ase.”
H2N
O
C
Urea amidohydrolase
NH2
1
2
1. Substrate
2. Functional Group
3. Reaction
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3
2 NH3 + CO2
Urea
Amide
Hydrolysis
3–47
16.14 Names and Classification
Enzymes are named by the type of reaction they
catalyze:
1. Oxoreductases
Oxidation-reduction reactions
2. Transferases
Move functional groups
3. Hydrolases
Hydrolysis reactions
4. Lyases
Addition across double bonds
or the reverse (elimination)
5. Isomerases
Rearrange the substrate
6. Ligases
Formation of bonds with
ATP cleavage
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16.14 Names and Classification
Like other proteins, enzymes can be simple
or conjugated.
Simple enzymes contain only amino acid
residues. More than one chain may be
present.
Conjugated enzymes have components
that are not made up of amino acids.
These can be organic or inorganic.
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3–49
16.14 Names and Classification
Conjugated enzymes consist of two parts:
An apoenzyme is the protein portion of a
conjugated enzyme.
A cofactor is the nonprotein portion of a
conjugated enzyme. There are three
types:
Prosthetic groups
Coenzymes
Minerals
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3–50
16.14 Names and Classification
Prosthetic groups, e.g. heme, are tightly
bound to the apoenzyme.
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16.14 Names and Classification
Coenzymes are small organic molecules that
are not tightly bound to the apoenzyme.
They are often derived from vitamins.
O
O
C
C
OH
N
Niacin,
Vitamin B3
H
H
O
C
NH2
NH2
N
N
R
R
NAD+
NADH
NAD+ and NADH are cofactors for many oxoreductases
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16.14 Names and Classification
Minerals are inorganic ions that act as
cofactors.
Common minerals:
Zn2+
Mg2+
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Mn2+
Fe2+
Cl1
3–53
16.15 How Enzymes Work
In catalysis, the substrate fits into the active
site of the enzyme, where it is held in place
while the reaction occurs.
E
enzyme
+
S
ES
E
substrate
complex
enzyme
+
P
product
This is called the enzyme-substrate complex,
or ES complex. The reaction may then take
place.
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3–54
16.15 How Enzymes Work
The active site is often
a crevice-like region
into which the substrate fits to form the
ES complex.
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3–55
16.15 How Enzymes Work
The active site is often
a crevice-like region
into which the substrate fits to form the
ES complex.
The specificity of enzymes for substrates
is attributed to the
structures of active
sites.
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3–56
16.15 How Enzymes Work
The “lock and key” model involves an active site
with a fixed shape that accommodates only a
certain substrate.
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3–57
16.15 How Enzymes Work
The “induced fit” model involves flexible active
site that adapts to the structure of the substrate and binds to it.
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3–58
16.16 Enzyme Activity
Enzymes activity is the rate at which an enzyme
converts substrate to product.
“Turnover rate,” substrate molecules/minute
or substrate molecules/second per
molecule of enzyme
“Turnover time,” seconds per molecule of
product per molecule of enzyme
Enzyme International Unit (EIU), concentration of enzyme that catalyzes 10–6 mole
of substrate reaction per minute
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3–59
16.16 Enzyme Activity
Enzyme-catalyzed reactions are fast!
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3–60
16.16 Enzyme Activity
All chemical reaction
rates increase with
temperature. With
enzymes, body temperature is optimal.
At higher temperatures, the enzyme
is denatured.
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3–61
16.16 Enzyme Activity
Acidity affects enzyme
acitivity.
Optimal pH for most
enzymes is 7.0 to 7.5.
Some digestive enzymes function best
outside this range.
Extremes in pH will
denature the enzyme.
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3–62
16.16 Enzyme Activity
All chemical reaction
rates increase with
increases in reactant
and catalyst concentration.
If enzyme concentration is constant, rate
will increase with substrate concentration to
a maximum.
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3–63
16.16 Enzyme Activity
Reaction rate will increase if enzyme
concentration is
increased.
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16.16 Enzyme Activity
Enzyme activity can be reduced by inhibitors.
Inhibition may be caused by a substance
that occurs naturally in an organism to
regulate enzyme activity. It may also be
caused by a medicine or a poison.
Enzyme inhibition can be irreversible or
reversible.
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3–65
16.16 Enzyme Activity
Irreversible inhibitors form a covalent bond
with a specific functional group of the
enzyme and deactivate it. Cyanide binds
to Fe3+ in cytochrome oxidase, so it can’t
carry oxygen. Heavy metals bind to thiols.
Cyt Fe3+
+
O2
cytochrome
oxidase
Cyt Fe3+
CytFeO23+
reversible complex
+
CN1
CytFeCN2+
stable complex
1  +
2
CN
S
O
2
3
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SCN1
+
SO32
3–66
16.16 Enzyme Activity
Some antibiotics inhibit bacterial enzymes.
Penicillin inhibits a transpeptidase that is
used in bacterial cell wall construction.
Sulfa drugs interfere with synthesis of folic
acid, which is required for growth of some
bacteria. Folic acid is also essential to animals, but we get it in our diet. However,
we need our intestinal bacteria! That’s why
some antibiotics cause digestive distress.
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16.16 Enzyme Activity
Reversible inhibitors bind reversibly to enzymes.
The enzyme-inhibitor complex is in equilibrium
with its components.
Enzyme + Inhibitor
EI complex
Shifting the equilibrium frees the enzyme.
There are two types of reversible inhibition,
competitive and noncompetitive.
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3–68
16.16 Enzyme Activity
Competitive inhibitors bind to the active site of
an enzyme and block it. They compete with
the substrate molecules for the active site.
Noncompetitive inhibitors bind reversibly to an
enzyme, but not at the active site. The
inhibitor alters the shape of the active site.
The enzyme cannot bind to the substrate.
Feedback inhibitors are metabolic products
that inhibit enzymes that catalyze their
production. They can be competitive or
noncompetitive.
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3–69