PROTEINS

Peptides
 An unbranched chain of amino acids, each joined to the next by a peptide bond

 Peptide bonds
 A covalent bond between the carboxyl group of one amino acid and the amino group of another
amino acid
o Dipeptide – a compound containing two amino acid residues
o Tripeptide – three amino acids
o Oligopeptide – peptides with 10-20 amino acid residues
o Polypeptide – a long unbranched chain of amino acids
o Protein – a peptide in which at least 40 amino acid residues are present
 Amino acid residue
 The portion of an amino acid structure that remains, after the release of H2O, when an amino acid
participates in peptide bond formation as it becomes part of a peptide

 Backbone of the peptide

 The repeating sequence of peptide bonds and α-carbon –CH group in a peptide

 Exercise: Draw the structural formula for the tripeptide Ala-Gly-Val

o Solution 1: The N-terminal end of the peptide involves alanine. Its structure is written first

o Solution 2: The structure if glycine is written to the right of the alanine structure, and a peptide
bond is formed between two amino acids by removing the elements of H2O and bonding the N of
glycine to the carboxyl C of the alanine

o Solution 3: To the right of the just-formed dipeptide, draw the structure of valine. Then repeat Step
2 to form the desired tripeptide
Peptide Nomenclature

IUPAC rules for naming small peptides are as follows:

Rule 1: The C-terminal amino acid residue (located at the far right of the structure) keeps its full amino acid name
Rule 2: All of the other amino acid residues have names that end in –yl. The –yl suffix replaces the –ine or –ic acid
ending of the amino acid name, except for tryptophan (tryptophyl), cysteine (cysteinyl), glutamine (glutaminyl),
and asparagine (asparaginyl)
Rule 3: The amino acid naming sequence begins at the N-terminal amino acid residue
 Exercise: Assign the IUPAC names of each of the following peptides
a. Glu-Ser-Ala
b. Gly-Tyr-Leu-Val

Isomeric Peptides
 Peptides that contain the same amino acids but in different order are different molecules with different
properties
 Give different biochemical responses
 The number of constitutional isomers is given by n! (n factorial)

Naturally Occurring Peptides

1. Dipeptide
a. Anserine
 Amino acids: alanine and histidine
 Found in human skeletal muscle
 Activates myosin ATPase activity
 Chelate copper and enhance copper activity
b. Aspartame
 Commercially synthesized dipeptide L-aspartylphenylalanyl methyl ester
 An artificial sweetener
2. Tripeptide
a. Glutathione
 Amino acids: Glutamic acid, cysteine, and glycine
 The sulfhydryl group from cysteine serves as active group
 Plays a major role in the oxidation-reduction reaction
 Decomposes H2O2 and maintains the integrity of cells and keeps hemoglobin in reduced state
3. Pentapeptide
a. Enkephalins
 Neurotransmitters produced by the brain itself that bind receptor sites in the brain to reduce pain
 Metenkephalin: Tyr-Gly-Gly-Phe-Met
 Leuenkephalin: Tyr-Gly-Gly-Phe-Leu
4. Nonapeptide
a. Vasopressin
 Aka ADH (antidiuretic hormone)
 Regulates excretion of water by the kidneys
 Affects blood pressure
b. Oxytocin
 Regulates uterine contractions and lactation

General Characteristics of Proteins

 Monomeric protein – a protein in which only one peptide chain is present
 Multimeric protein – a protein in which more than one peptide chain is present
o Protein subunits – peptide chains present in multimeric proteins
 Simple protein – a protein in which only amino acid residues are present
  Conjugated protein – a protein that has one or more non-amino acid entities present in its structure in
addition to one or more peptide chains
o Prosthetic group – a non-amino acid group present in a conjugated protein
Class Prosthetic Group Specific Example Function
Hemoglobin Carrier of O2 in blood
Hemoproteins Heme unit
Myoglobin Oxygen binder in muscles
LDL
Lipoproteins Lipid Lipid carrier
HDL
Gamma globulin Antibody
Mucin Lubricant in mucous
Glycoproteins Carbohydrate
secretions
Interferon Antiviral protection
Glycogen phosphorylase Enzyme in glycogen
Phosphoproteins Phosphate group
phosphorylation
Ribosomes Site for protein synthesis
Nucleoproteins Nucleic acid Viruses Self-replicating infectious
complex
Iron – ferritin Storage complex for iron
Metalloproteins Metal ion
Zinc – alcohol dehydrogenase Enzyme in alcohol oxidation

1. Primary structure
 The order in which amino acids are linked together in a protein
 Involves number, kinds, and order of amino acids
 Insulin – the first protein for which the primary structure was determined; the sequencing was
completed in 1953 by Frederick Sanger
 Amino acids are linked together by a peptide bond in a specific sequence to form a polypeptide
chain

2. Secondary structure
 The arrangement in space adopted by the backbone portion of a protein
 The regularly repeating ordered spatial arrangements of amino acids near each other in the protein
chain, which results from the hydrogen bonds between carbonyl oxygen atoms and amino acid
hydrogen atoms
a. Alpha helix
 A protein secondary structure in which a single protein chain adopts a shape that resembles a
coiled spring, with coil configuration maintained by hydrogen bonds between every fourth
amino acid
 Proline disrupts the α-helix because its α-imino group has no free hydrogen to contribute to the
stabilizing hydrogen bonds
 b. Beta pleated sheet
 A protein secondary structure in which two fully extended protein chain segments in the same
or different molecules are held together by hydrogen bonds
 Hydrogen bonds may occur between two side-by-side chains, or a single chain that is folded
back on itself

3. Tertiary structure
 The overall three-dimensional shape of a protein that results from the interactions between amino
acid side chains that are widely separated from each other within a peptide
 Interactions Responsible for Tertiary Structure
a. Covalent disulfide bond
 The strongest of the tertiary-structure interactions
 Result from the –SH groups of two cysteine residues
b. Electrostatic interactions (salt bridges)
 Always involve the interaction between an acidic side chain and a basic side chain
c. Hydrogen bonds
 Occur between amino acids with polar R groups especially those that possess the following
functional groups: hydroxyl, amino, carboxyl, amide
d. Hydrophobic interactions
 Result when two nonpolar side chains are close to each other
4. Quaternary structure
 The highest level of organization among various peptide chains in a multimeric protein
 The three-dimensional shape of a protein consisting of two or more independent peptide chains,
which results from noncovalent interactions between R groups
 Interactions involved: electrostatic interactions, hydrogen bonds, hydrophobic interactions

Protein Denaturation
 Protein hydrolysis – the reverse of the reaction formation for a peptide bond where free amino acids are
produced when protein or small peptide in a solution of strong acid or base is heated
 Protein denaturation – is the partial or complete disorganization of a protein’s characteristic three-
dimensional shape as a result of disruption of its secondary, tertiary, and quaternary structural interactions
 Coagulation – the precipitation out of biochemical solution of denatured protein
 Cauterization – heat induced denaturation used to seal small wounds during surgery
Denaturing Agent Mode of Action
Heat  Disrupts hydrogen bond by making molecules vibrate too violently
 Produces coagulation, as in frying of egg
Microwave radiation  Causes violent vibrations of molecules that disrupt hydrogen bonds
Ultraviolet radiation  Similar to heat (sunburn)
Violent whipping or shaking  Causes molecules in globular shapes to extend to longer lengths,
which then entangle
 Detergent  Affects R-group interaction
Organic solvents  Interfere with the R-group interactions because these solvents also
can form hydrogen bonds
Strong acids & bases  Disrupts hydrogen bonds and salt bridges; prolonged action leads
to actual hydrolysis of peptide bonds
Salts of heavy metals  Metal ions combine with –SH groups and form poisonous salts
Reducing agents  Reduce disulfide linkages to produce –SH groups

Protein Classification Based on Shape

 Fibrous proteins
 A protein whose molecules have an elongated shape with one dimension much longer than the
others
 Have a simple, regular, linear structures
 Globular proteins
 A protein whose molecules have peptide chains that are folded into spherical or globular shape
 Membrane proteins
 A protein that is found associated with a membrane system of a cell

Fibrous vs. Globular Proteins

Fibrous Globular
Water solubility Insoluble Soluble
Type of secondary structure Single type Multiple types
General function Provides support and external Metabolic functions such as catalysis,
protection transport, and regulation
 The number of kinds of globular proteins far exceed the number of kinds of fibrous protein
 The total mass of fibrous proteins present exceeds the total mass of globular proteins

Some Common Fibrous and Globular Proteins

Name Occurrence and Function
Fibrous proteins
Keratin Wool, feather, hooves, silk, and fingernails
Collagen Tendons, bone, and other connective tissue
Elastin Blood vessels and ligaments
Myosin Muscle tissue
Fibrin Blood clots
Globular proteins
Insulin Regulatory hormone for controlling glucose metabolism
Myoglobin Oxygen storage in muscles
Hemoglobin Oxygen transport in blood
Transferrin Iron transport in blood
Immunoglobulin Immune system responses

Protein Classification Based on Function

1. Catalytic proteins
 Aka enzymes
 Participate in almost all of the metabolic reactions that occur in cells
2. Defense proteins
 Aka immunoglobulins or antibodies
 Central to the functioning of the body’s immune system
 They bind to foreign substances, such as bacteria and viruses, to help combat invasion of the body
by foreign particles
3. Transport proteins
 Bind to particular small biomolecules and transport them to other locations in the body
  Hemoglobin – carries oxygen from lungs to other organs and tissues
 Ferritin – carries iron from the liver to the bone marrow
 HDL & LDL – carriers of cholesterol in the bloodstream
4. Messenger proteins
 Transmits signals to coordinate biochemical processes between different cells, tissues, and organs
 Examples: hormone
5. Contractile proteins
 Necessary for all forms of movement
 Examples: contractile proteins
6. Structural proteins
 Confer stiffness and rigidity to otherwise fluid-like biochemical systems
 Example: collagen and keratin
7. Transmembrane proteins
 Span the cell membrane help control the movement of small molecules and ions through the cell
membrane
8. Storage proteins
 Bind and store small molecules for future use
 Ferritin – storage form of iron
 Myoglobin – oxygen storage protein present in muscle
9. Regulatory proteins
 Often found “embedded” in the exterior surface of cell membranes
 They act as sites at which messenger molecules, including messenger proteins can bind and initiate
the effect that the messenger “carries”
10. Nutrient proteins
 Particularly important in early stages of life
 Examples: Casein (milk) and ovalbumin (eggs)

Examples of Medically Important Proteins

1. Collagen
 The most abundant of all proteins in humans and is the major structural material in tendons,
ligaments, blood vessels, skin, bones and teeth
 The predominant structural feature within is a triple helix

 Tropocollagen – the basic, structural unit of collagen

 Ascorbic acid – promotes hydroxylation of proline and lysine in collagen
 Collagen Types
a. Type I: skin, bones, tendon, cornea
b. Type II: cartilage, intervertebral disk
c. Type III: blood vessels, lymph nodes, dermis, early phases of wound repair
d. Type IV: flexible, sheetlike networks and is present in all basement membrane
e. Type X: epiphyseal plate

 Collagen Disorders
a. Ehlers-Danlos syndrome
 Caused by mutations in α-chains, resulting in abnormalities in collagen structure, synthesis,
secretion, or degradation
 Associated with hyperextensive joints, hyperelastisity of skin, aortic dissection, rupture of the
colon, and vessel instability resulting in skin hemorrhages
 Affected collagen types: I and III