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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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16.2 Amino AcidsAn 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.
CCN
RH
O
O
H
HH
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16.2 Amino AcidsThere are 20 standard amino acids, each
with a different R group. There are four categories of amino acids.
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16.2 Amino AcidsPolar neutral amino acids.
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16.2 Amino Acids
Polar acidic and basic amino acids.
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16.2 Amino Acids
Polar acidic and basic amino acids.
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16.2 Amino AcidsTen 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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16.3 HandednessThe -carbon in an amino acid is chiral. Most
amino acids have the L-configuration.
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16.4 Acid-Base PropertiesAmino acids undergo intramolecular proton
transfer. They always exist as zwitterions (double, or hybrid) ions.
Zwitterions have no net electrical charge.
CCN
RH
O
O
H
H CCN
RH
O
O
H
HH
H
Neutral Molecule Zwitterion
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16.4 Acid-Base Properties
In acidic solution, the carboxylate group is protonated. This produces a cation.
CCN
RH
O
O
H
HH
+ H3O CCN
RH
O
OH
H
HH
+ H2O
Zwitterion + acid Positive net charge
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16.4 Acid-Base Properties
In basic solution, the ammonium group is deprotonated. This produces an anion.
CCN
RH
O
O
H
HH
+ OH
Zwitterion + base
CCN
RH
O
OHH
+ H2O
Negative net charge
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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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16.5 Peptide FormationAmino acids condense to form amide, or
peptide, bonds. The reactions are cat-alyzed by enzymes.
N C C
H
R1
O
O
H
H
H
+ N C C
H
R2
O
O
H
H
H
N C C
H
R1
O
N
H
H
H
H
C
H
R2
C
O
O
+ H2O
enzyme
a dipeptide
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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 BiologyProtein synthesis is directed by RNA (ribonu-
nucleic acid). DNA (deoxyribonucleic acid) acts as a template for RNA synthesis.
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16.6 - 16.10 Protein Structure
The structure of pro-teins and peptides is critical to their func-tion 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 StructureThe structure of pro-
teins and peptides is critical to their func-tion in organisms. It is divided into four levels.
Primary structure of proteins refers to the sequence of amino acid residues. The illustration shows hu-man myobglobin.
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16.6 - 16.10 Protein Structure
Secondary structure of proteins refers to the arrangement adopted by the backbone por-tion 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 hydro- gen 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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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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16.6 - 16.10 Protein Structure
Tertiary structure re-fers to the overall three-dimensional shape of a protein.
This illustration shows the struc-ture 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 StructureDisulfide bonds form between –SH groups of
cysteine residues. They are covalent bonds.
C
C CH2H
N
O
SH
H
C
C H
N
O
H
CH2+ HSenzyme
C
C CH2H
N
O
S
H
C
C H
N
O
H
CH2S
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16.6 - 16.10 Protein StructureDisulfide 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 ammo-nium ions are ionic bonds. They are also called salt bridges.
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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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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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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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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 ClassificationClassifications 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
isomer- ization of retinal, a molecule derived from Vitamin A.
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16.11 Protein Functions
7. Movement: Proteins in muscle are respon- sible for contraction and relax- ation.
Actin and myosin are fibrous proteins that slide
across each other in muscle movement.
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16.11 Protein Functions
8. Transport: Proteins transport ions and mol- ecules 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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16.12 Protein Deactivation
Proteins can be deactivated by two processes, hydrolysis and denaturation.
Hydrolysis is the reverse of peptide bond for-mation. It reduces a protein to smaller poly-peptide molecules and free amino acids.
Hydrolysis can be caused by enzymes or strong acids or bases. It is part of the nor-mal digestion of proteins in the stomach.
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16.12 Protein Deactivation
Hydrolysis of a tripeptide to amino acids:
N C C
H
R1
O
N
H
H
H
H
C
H
R2
C
O
N
N C C
H
R1
O
O
H
H
H
+ N C C
H
R2
O
O
H
H
H
acid, base,or enzyme
H
C
R3
H
C
O
O
H2O
+ N C C
H
R3
O
O
H
H
H
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16.12 Protein Deactivation
Denaturation is the partial or complete disorganization of a protein’s three-dimensional shape.
Denaturation is caused by disruption of the attractive forces that produce this shape. Heat, acids or bases, deter-gents, organic solvents, ions of heavy metals, and violent whipping or shaking can denature proteins.
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16.12 Protein DeactivationDenaturation 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 reac-tion 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.”
1. Substrate Urea 2. Functional Group Amide 3. Reaction
Hydrolysis
H2NC
NH2
O Urea amidohydrolase
1 2 32 NH3 + CO2
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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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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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16.14 Names and ClassificationProsthetic groups, e.g. heme, are tightly
bound to the apoenzyme.
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16.14 Names and ClassificationCoenzymes are small organic molecules that
are not tightly bound to the apoenzyme. They are often derived from vitamins.
N
COH
O
N
CNH2
O
R
N
C
R
H H O
NH2
Niacin,Vitamin B3 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+ Mn2+ Fe2+ Cl1−
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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.
This is called the enzyme-substrate complex, or ES complex. The reaction may then take place.
E + S ES E + P
enzyme substrate complex enzyme product
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16.15 How Enzymes Work
The active site is often a crevice-like region into which the sub-strate fits to form the ES complex.
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16.15 How Enzymes Work
The active site is often a crevice-like region into which the sub-strate fits to form the ES complex.
The specificity of en-zymes for substrates is attributed to the structures of active sites.
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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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16.15 How Enzymes Work
The “induced fit” model involves flexible active site that adapts to the structure of the sub-strate and binds to it.
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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), concentra- tion of enzyme that catalyzes 10–6 mole of substrate reaction per minute
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16.16 Enzyme Activity
Enzyme-catalyzed reactions are fast!
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16.16 Enzyme Activity
All chemical reaction rates increase with temperature. With enzymes, body tem-perature is optimal.
At higher temper-atures, the enzyme is denatured.
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16.16 Enzyme ActivityAcidity affects enzyme
acitivity.
Optimal pH for most enzymes is 7.0 to 7.5.
Some digestive en-zymes function best outside this range.
Extremes in pH will denature the enzyme.
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16.16 Enzyme ActivityAll chemical reaction
rates increase with increases in reactant and catalyst concen-tration.
If enzyme concentra-tion is constant, rate will increase with sub-strate concentration to a maximum.
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16.16 Enzyme Activity
Reaction rate will in-crease 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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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+ + CN1− Cyt⏐ Fe⏐ CN2+
cytochromeoxidase
stable complex
CN1− + S2O32− SCN1− + SO3
2−
thiosulfate thiocyanate sulfite
Cyt ⏐ Fe3+ + O2 Cyt⏐ Fe⏐ O23+
reversible complex
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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 an-imals, 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.
Shifting the equilibrium frees the enzyme.There are two types of reversible inhibition, competitive and noncompetitive.
Enzyme + Inhibitor EI complex
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16.16 Enzyme ActivityCompetitive 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.