Molecules, Gene and

disease

Session 1

Lecture 2

Amino acids and protein

Structural Features of Amino Acids

• All 20 of the common amino acids are α-amino acids.

• They have a carboxyl group and an amino group bonded to the same

carbon atom (the α-carbon)

• They differ from each other in their side chains, or R groups

• R groups are vary in structure, size, and electric charge, and which

influence the solubility of the amino acids in water.

• The α-carbon atom is a chiral center; so, amino acids have two possible stereoisomers, L or D

• The Amino Acid Residues in Proteins Are L Stereoisomers

Cells are able to specifically synthesize

the L isomers of amino acids because

the active sites of enzymes are

asymmetric, causing the reactions they

catalyze to be stereospecific.

Classification of Amino Acids by R Group1. Nonpolar, aliphatic R groups

2. Aromatic R Groups

3. Polar, uncharged R groups

4. Positively Charged (Basic) R Group:

5. Negatively Charged (Acidic) R Groups

Amino acids classification based on nutritional requirement:

• Isoleusine, leusine, theronine, lysine, methionin, phenylalanine, tryptophan, and valine are essential amino acids. There carbon skeleton cannot be synthesized by human being, so these amino acids must be taken in food for normal growth.

• Histidine and argentine are essential for growing children not for adults so these are semi- essential.

• The remaining 10 amino acids are nonessential, because there carbon skeleton can be synthesized by the body.

Acid- Base Behavior of Amino acids

The acid base properties of amino acids depends on the:

*amino and carboxyl groups attached to the α- carbon

and *on the basic, acidic, or other functional

groups represented by R.

Acid- Base Behavior of Amino acids*In the physiological pH range of 7.35- 7.45, the carboxyl group of an amino acid is dissociated and the amino group is protonated, it is called Dipolar ion or ampholyte, or zwitter ion

Acid- Base Behavior of Amino acids

Acid- Base Behavior of Amino acids

• At low pH an amino acid is in its cationic form with both its amino and carboxyl groups are protonated (NH3

+ and COOH).• As the pH rises, the carboxyl group loses its

proton and the ampholyte form appear at about pH 6.

• With a further increase in pH the amino group (NH3

+ ) is deprotonated, resulting in the anionic form of the molecule.

Alanine

Titration of amino acids:

Amino acids with ionizable R groups have additional ionic

species, depending on the pH of the medium and the pKa of the

R group.

•

Iso electric point of amino acids

• The pH at which amino acid bears no net charge and therefore does not move in an electric field, is called isoelectric pH (pI).

• The characteristic pH at which the net electric charge is zero is called the isoelectric point or isoelectric pH, designated pI. For glycine, which has no ionizable group in its side chain, the isoelectric point is simply the arithmetic mean of the two pKa values:

• One of the most Important Reactions of Amino Acids is

the formation of peptide bond

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Peptide Bonds Are Planar. In a pair of linked amino acids, six atoms (C α , C, O, N, H, and C α ) lie in a plane. Side chains are

shown as green balls.

Peptide Bonds Are Planar. In a pair of linked amino acids, six atoms (C α , C, O, N, H, and C α ) lie in a plane. Side chains are

shown as green balls.

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Trans and Cis Peptide Bonds. The trans form is strongly favored because of steric

clashes that occur in the cis form

Trans and Cis Peptide Bonds. The trans form is strongly favored because of steric

clashes that occur in the cis form

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Key feature of the peptide bond:

• All the atoms of the bond are in the same plane

• No rotation about the peptide binds due to double bond characteristics

• Carbonyl oxygen and Amide hydrogen are in the trans orientation

The peptide has a directionThe peptide has a direction

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The pentapeptide serylglycyltyrosylalanylleucine,

Peptides are named beginning with the aminoterminal residue, which by

convention is placed at the left.

The pentapeptide serylglycyltyrosylalanylleucine,

Peptides are named beginning with the aminoterminal residue, which by

convention is placed at the left.

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Peptides Can Be Distinguished by TheirIonization Behavior

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Example: Alanylglutamylglycyllysine. This tetrapeptide has one free -amino group, one free -carboxyl group, and two ionizable R groups. The groups ionized at pH 7.0 are in red

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Proteins

Proteins are polypeptides Linear chains of 20 different amino acids, in a sequence encoded by the gene

The polypeptide chain folds into a complex and highly specific three-dimensional structure, determined by the sequence of amino acids

The folding of proteins depends on the chemical and physical properties of the amino acids

. Chemical Nature and function of proteins

• The amino acids that make up a protein contribute to the folding and function of that protein. The side chains those of the amino acids are more important in a polypeptide as they contribute to the charge seen on the protein.

The isoelectric point (pI) of protein

• The isoelectric point (pI) is the pH at which a protein has no overall net charge.

• Acidic proteins contain many negatively charged amino acids and have a low pI

• Basic proteins contain many positively charged amino acids and have a high pI

Proteins play crucial roles in virtually all biological processes, as : Catalysts - enzymes

Machines – e.g., muscular contraction and motion

Structural support (e.g., collagens in skin and bone)

Immune protection (e.g., immunoglobulins)

Ion channels

Receptors (for hormones, neurotransmitters, etc.)

Ligands in cell signalling (growth factors etc.)

Transporters (e.g. O2, Fe)

Summary