Proteins are naturally occurring polypeptides.

Polypeptides are copolymers of amino acids, meaning

different amino acids are joined in a specific sequence. Proteins constitutes about half of the body’s dry
weight. Thousands of proteins, each with a specialized biological function are classified in the table
below.

Classification of Proteins by Biological functions

Class Biological functions
Contractile protein Contracts and expands to give
motion
Defense protein Protection against viruses,
bacteria, other foreign bodies
Enzyme Catalysis of virtually all
reactions in living organism
Regulatory protein Regulation and control of cell
processes
Storage protein Store nutrients for organism
Structural protein Mechanical support for
organism’s structure
Transport protein Transports chemicals in
bloodstream and cells
Examples
Muscle(actin,myosin)
Antibodies(immunoglobulins)
Blood clotting(thrombin and
fibrinogen)
Toxic proteins(snake venom)
Peptide and lipid
digestion(peptidase, esterase)
Metabolism(insulin,parathyroid
hormone)
Skeletal growth(growth
hormone)
Neurotransmitters(enkephalin,
dopamine)
Seed proteins for green plants
Egg white protein(ovalbumin)
Milk protein(casein)
Iron storage in spleen(ferritin)
Feathers, hair, hoof, horn, skin,
wool(α-keratin)
Bone,cornea,tendons and other
connective tissue(collagen)
Blood vessels,ligaments(elastin)
Blood clots(fibrin)ic
Oxygen(hemoglobin)
Lipids(lipoproteins)
Active transport by integral
proteins

*Amino acids as building blocks of polypeptides(proteins)

* acids contain both an amine(basic) and carboxyl group(acid) in the same molecules, hence ampholytes
* acids used to synthesize polypeptides in nature are the α-amino acids, i.e., the amino group is attached
to the first carbon attached to the COOH. Other amino acids exist as β-amino acid, γ - amino acids.
What does a simple amino acid refer to?
*The only amino acids used in polypeptide synthesis for species of plants and animals are the 20 α-
amino acids.
*10 essential amino acids(EAA) for human: are not synthesis in the body, therefore they must be
provided by dietary intake HIMPVTTALL PVT TIM HALL
*Amino acids differ on their side chain R, which is used to group them in four categories as shown in the
first column:
(1) nonpolar neutral amino acid have hydrophobic R groups (aliphatic chains or aromatic rings)
(2) polar neutral amino acids have hydrophilic R group(contain (-OH), Sulfur or amide)
(3) Polar acidic amino acid have hydrophilic acidic R groups(COOH). This is apart from the COOH in the
backbone
(4) Polar basic amino acids have R group that contain basic amino group. This is in addition to the NH2 in
the backbone of the amino acid

Two important exceptions in the above rules;

1. Tyrosine contain aromatic group and an -OH and is considered polar neutral.
2. Methionine contains sulfur as a part of the R group. Sulfur and carbon have the same
electronegativity. Methionine, therefore, is considered nonpolar.
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Common names which are more convenient than the IUPAC names are indicated in the first column.
Three letters and single letter symbols; R side chain groups and isoelectric points are reflected in the
other columns.
Activity: Answer the following questions
1. Enumerate the amino acids whose three letter symbol are the first three letters in their common
names.
 2. How many amino acids contain the first letter and two other letters in their common names?
3. Identify the amino acids with single letter symbol different from the first letter in their common
name.
4. Identify the amino acid whose side group R forms a ring with other part of the backbone of the
amino acid?
5.

Amino acids general formula is

 NH2-CHR- COOH

The general formula reflects a neutral uncharged molecule. Amino acids do not exist in this form. They
undergo acid-base reaction where an H+ is transferred from COOH to the amine nitrogen to form a
dipolar ion referred to as zwitterion. This contains carboxylate and ammonium ionic centers but has a
net charge of ZERO.

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Cation/positive ion negative ion

Acidic media basic media
Low pH -acidic high pH12 basic
High [H+] low [H+]

*The relative amounts of the three species depend on pH and is quantified by the isoelectric point, pI, of
an amino acids.
*Isoelectric point, pI, is the pH at which an amino acid has net zero charge.
*pH vs pI of neutral amino acids(narrow range of pI 5.05-6.30)
In acidic media: pH< pI shift to left/ neutral amino acids are cationic(positive)
In basic media: pH>pI shift to the right? Neutral a.a. are negative ions
 At 2 pH units to either side of pI: 98% of neutral a.a. are in zwitterion form. The
structural changes resist pH changes for neutral amino acid since their solution act as
buffers. The pI depends on the basicity(-NH2) and acidity (-COOH) which in turn
depend on the electron withdrawing or electron releasing character of the R group.

pI computation:
*For neutral amino acids: pI = (pKa1 + pka2)/2
*for amino acids with an NH2 or COOH in their R group, expect three pka values to be
given.
Hint:
1. draw a number line where to indicate the pKa values
2. the structure of the amino acids in the ranges and determine their charges. The
charges decrease by one unit from the left
3. Zwitterion has a net charge of zero. To compute for the pI, take the average of
pKa adjacent to the zwitterion.

Electrophoresis: an analytical method for identifying amino acids by observing their

migration as a function of pH under an applied electric field gradient.

Ninhydrin + amino acid → blue purple color

At pI: no migration
pH<pI: amino acid with positive charge migrate to the cathode
pH>pI: amino acid with negative charge migrate to the anode.

Materials: paper, polyacrylamide gel, ninhydrin as indicator.youtube

1. For glycine: pka1 of COOH = 2.34 and pKa2 of NH2 group=9.60

therefore, pI (glycine) = (2.34+9.60)/2 = 5.94.

Exercises:
1. What is the structure and net charge of neutral amino acid at pH=pI?
Physiological pH is near pH 7.
pH blood= 7.5
in other cell, pH = 6.8-7.1
Therefore, neutral amino acids at pH=pI are in zwitterion form.
2. What is the structure of Asp at pH= 2.77?
 3. Calculate the pI of lysine given pka COOH= 2.8, pKa NH2= 8.95 and pKa NH2 in
the R group= 10.53.
4. Calculate the pI of aspartate given pKa1= 1.20, pKa2= 3.32 and pKa3= 9.6

Peptide formation. Dehydration between -COOH one one a.a. and -NH2 of other amino
form a peptide bond. Peptide bond is a single bond, however, it is a strong bond
because it has a double bond character.

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Terminals of polypeptide:
N terminal contains -NH2 is on the far left of the chain.
C terminal contains -COOH is on the far right of the chain.
 This Photo by Unknown Author is licensed under CC BY-NC

Prefixes indicates the number amino acid in a chain/residue.

Dipeptide- 2 a.a.
Tripeptide- 3 a.a.
Tetrapeptide- 4 a.a.
Oligopeptide: < 10 a.a. residues
Polypeptide

Number of isomers of polypeptide containing n amino acid residues: n !

Example:
A tripeptide contain Asp, Phe, Ala.
a) How many isomers are possible? Answer: n! = 3! = 3.2.1 = 6 isomers
b) Write the six isomers:

c)Are the six isomers the same?

Board Exam: A polypeptide is cleaved by enzymes. What are the fragments called?
a) Peptane b) dipeptide c) oligopeptide d) residue

Structural relationship: attractive interaction between the side chain of a.a.

1. Phenylalanine and Leucine;
C6H5-CH2- Vs (CH3)2CH-CH2CH2-

Hydrophobic attraction
2. Glu and leu:
HOOC-CH2CH2- Vs (CH3)2CH-CH2CH2-
Polar nonpolar
 No interaction
3. Glu and Lys
-CH2CH2COO- H3NCH2CH2CH2CH2-
Ionic interaction salt bridge
4. Asp and Ser
-CH2COOH Vs HOCH2- H bonding

5. Cys and Cys -CH2SH HS-CH2-

-CH2S –S CH2- disulfide linkage
6. Glu and glu
HOOC-CH2CH2- no interaction because of repulsion

Protein structure
1.Primary structure is stabilized by a peptide bond connecting amino acids. All peptide
bonds are in trans configuration

2.Secondary structures to local folded structures that form within a polypeptide due to
interactions between atoms of the backbone.
Α-helix:. the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-
H) of an amino acid that is four down the chain. intermolecular H bonding results in a
turn; rise of 1.5 Angstrom/ amino acid or 5.4 Angstrom per loop

proline is “helix breaker” because its unusual R group creates a bend in the chain

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Beta-pleated sheets structure: stabilized by intermolecular H bonding. Beta-pleated

sheets may be parallel or anti-parallel
a)parallel: amino acid run in the same direction
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b)anti-parallel: opposite direction

amino acids with large ring structure in their R groups such as tryptophan, tyrosine, and
phenylalanine, are often found in β pleated sheets
Proteins with secondary structure
1. collagen type helix: consist of 3 intertwined chains, where the loop accounts for
a distance of 9 Angstrom with three amino acid in each loop
2. egg white lysozymes: 35% alpha helix, 10% pleated sheet, rest disordered.

3.Tertiary structures. This the overall three-dimensional structure of a polypeptide. This

structure is due to the interactions between R groups of the amino acids that make up
the protein.
R group interaction includes the following:
*Hydrogen bonding
between Hδ + and δ – oxygen or nitrogen
hydrogen bond between N-H and C=O
The energy stabilizing H bond is an enthalpy effect
*ionic interaction involve those with opposite charges(salt bridge)
*disulfide bonds, covalent linkage between cysteines are much stronger than other
bonds that contribute to the tertiary structure.
- S-----S—(intermolecular or intramolecular/insulin,vasopressin)
INTRAMURALS CARIG
UNIVERSITY MEET-inter-campus competition

London forces involve non-covalent bonds.

*repulsion of R groups with like charges
*Hydrophobic interactions among amino acids with nonpolar, hydrophobic R cluster
on the inside of the protein, leaving hydrophilic amino acids on the outside to interact
with surrounding water molecules. Major importance in the maintenance of tertiary
structure as it may stabilize alpha-helix and pleated sheets.

PROTEINS WITH QUATERNARY STRUCTURES

Effect of replacement of an amino acid in a polypeptide chain:

Sickle cell anemia is an inherited abnormality of hemoglobin
The 6th residue in the β polypeptide chain,
Glu is replaced by Val:
-CH2CH2COO- (salt bridge) → CH3( hydrophobic)

The destruction of the salt bridge results in a change of conformational structure.

The shape of the oxygenated hemoglobin from biconcave disk is altered to cresents.
The RBC clump together and reduce the flow capacity of capillaries.

Which group is most affected?

more common in certain ethnic groups:
People of African descent: African-Americans (1 in 12 carries a sickle cell gene)
Hispanic-Americans from Central and South America
Middle Eastern, Asian, Indian, and Mediterranean descent.
Discuss the effect of replacement of Glu with Asp

For additional learning materials. Take down notes

1.https://www.chemguide>organicprops>acid base
The acid-base behavior of amino acids
2.https://byjus.com>chem>amine
zwitterions