Introduction to Amino Acids

of Medical Importance

Amino acids

Amino Acids are the building blocks of proteins

ONLY 20 amino acids (out of 300 in nature) are present in

human body (that are coded for by DNA)

What are Amino Acids

What is an Amino Acid

• Amino acid is an organic acid which contains both an acidic carboxyl group (-COOH) and a basic amino group (-NH2).

• In most natural amino acids, the amino group is attached to the -a carbon atom i.e. the carbon atom adjacent to the carboxyl group So, they are called a amino acids

General formula of amino acids in humans COOH I a carbon

NH2 – C - H I R

There are 20 commonamino acids that make up

almost all proteins.

Each has a carboxyl group &an amino group bonded to

the same carbon atom.

Each has a different sidechain, or R group.

This Carbon is calledα-carbon

At physiological pH (approximately pH 7.4), in free amino acids:Carboxyl group is dissociated to (-COO-) & amino group is positively charged (-NH3+)

Classification of amino acids

• polar & non polar (according to the side chain properties)

• Essential & non essential (according to being synthesized or not )

• Glucogenic, ketogenic & both (according to metabolic fate)

• At physiological pH (approximately pH 7.4), in free amino acids: Carboxyl group is dissociated to (-COO-) & amino group is positively charged (-NH3+)

• In proteins almost all of these carboxyl & amino groups are combined in peptide bond Carboxyl & amino groups of peptide bond do not share in chemical reactions of amino acids EXCEPT for hydrogen bonding So, it is the nature of the side chains that determines the role of an amino acid in a protein.

Accordingly, amino acids are classified according to properties of their side chains i.e. whether they are polar or nonpolar

Classification of amino acids according to side chains properties

Amino acids with nonpolar side chains

• Each of these amino acids has a non-polar side chain that does not participate in hydrogen or ionic bonds

(i.e. hydrophobic : they do not bind with water)

• Location of nonpolar amino acids in proteins: in proteins found in aqueous solutions (a polar environment), the side chains

of the nonpolar amino acids tend to cluster together in the interior of the protein due to the hydrophobic nature of the nonpolar side chains (R-groups).

Accordingly, the nonpolar R-groups thus fill up the interior of the folded

protein

These side chains are nonpolar

& tend to cluster together

within proteins

stabilizing proteinstructure via hydrophobicinteractions

Amino acids with uncharged polar side chains

• These amino acids have zero net charge at neutral pH (uncharged)• They can form bonds (interactions) with water i.e. hydrophilic They are:• Serine, threonine & tyrosine each contains a polar hydroxyl group that can participate in hydrogen bond formation (so, they are hydrophilic) • Aspargine & glutamine each contains a carbonyl group & an amide group, both

of which can participate in hydrogen bonding. (so, they are hydrophilic)

• Cysteine contains sulfhydryl (–SH) group which are oxidized to form a dimer cystine that contains covalent cross-link called a disulfide bond –S-S-

The R groups of these amino acids

arehydrophilic because

they containfunctional groups that form H bonds

with water

Cysteine can be oxidized to form a covalently linked dimeric amino acid, cystine

Amino acids with negatively charged side chains

• Amino acids aspartic acid & glutamic acid have carboxyl groups (COOH) side chains

• At physiological pH, (-COOH) side chains of these amino acids are

negatively charged ( –COO-).

So, they are called acidic amino acids.

& are hydrophilic (polar) i.e. can form interaction (bond) with water.

• Amino acids lysine & argenine have amino group (-NH2) side chains

• At physiologic pH, (- NH2) side chains of these amino acids are positively charged(-NH3+).

So, they are called basic amino acids.

& they are hydrophilic (polar) i.e. can form interaction (bond) with water.

• Histidine is weakly basic.

Amino acids with positively charged side chains

Essential amino acids

These are amino acids that can NOT be synthesized in the human body.So, they MUST be supplied in diet.

They are:

Methionine Threonine

Valine Isoleucine

Phenylalanine Tryptophan

Leucine Lysine

Argenine & histidine are semi-essential amino acids (synthesized in the body in insufficient amounts)

Some important properties of amino acids

1- Optical activity of amino acids

- The a-carbon of each amino acid is attached to four different chemical groups (with exception of glycine , its a-carbon is attached to two hydrogen) - So, they can exist in two forms called as D & L that are mirror images of each other

- The two forms in each pair are termed sterioisomers, optical isomers or enantiomers

- All amino acids found in proteins are of the L-amino acids

- D-amino acids are found in some antibiotics, in plant & bacterial cell walls

D- & L- amino acids

2- The isoelectric point

• At certain pH, an amino acid form Zwitterion (dipolar ions) i.e. an ion carrying both negative & positive charge & hence, is electrically neutral.

• So, it will not migrate to cathode or anode • The pH at which a zwitterion is formed is called isoelectric point.

Each amino acid has its own isoelectric point

- At which, it carries zero net charge (+ve = -ve) & will not migrate to anode or cathode- Above which, amino acids will carry a negative charge - Below which, it will carry a positive charge .

Some Important Properties of Amino Acids (cont.)Some important properties of amino acids (cont.)

Introduction to Proteins

of Medical Importance

Importance of Proteins

1- Proteins form the building units of all body cells

2-Almost all enzymes are protein in nature

3- Many hormones are protein in nature as insulin and thyroxine 4- Certain biological compounds necessary for maintenance of life as hemoglobin, myoglobin etc are protein substances

5- Immnuoglobulins (antibodies) present in body are protein in nature

6- Osmotic pressure of plasma proteins is necessary for exchange of fluids between the blood and interstitial fluid

Structure of protein

Proteins have four levels of structure

Primary structure

Definition: is the sequence of amino acids in a protein.

Importance: for studying genetic diseases (that results from proteins of abnormal amino acid sequence i.e. abnormal primary structure)

Peptide bonds:

In proteins, amino acids are joined covalently by peptide bonds to form a polypeptide chainPeptide bonds: 1- formed by a linkage between a-carboxyl group of one amino acid and the a-amino group of adjacent amino acid 2- They are broken by enzymatic hydrolysis 3- They are not lost by denaturation

Polypeptide chain:

is a chain formed from joining of amino acids by peptide bonds leaving two free ends : the amino terminal or N-terminal (with free amino group) and a carboxyl terminal , C-terminal (with a free carboxyl group) . The sequence of a polypeptide chain starts from the amino terminal

Polypeptide Chain

Secondary structure

Definition: is the arrangement of adjacent amino acids that are located near to each other in the linear sequence (polypeptide)

Examples of these arrangements: a helix, b-sheet

a-helix: - A spiral structure - Each turn of a-helix contains 3-4 amino acids - Helix is stabilized by hydrogen bonds. -b-sheetComposed of segments of fully extended polypeptide chains joined with hydrogen bonding perpendicular to polypeptide backbone

Motifs (supersecondary structure):- Combining secondary structural elements (a-helix, b-sheets & nonrepetitive sequences)

- Combining of motifs will form a domain which is: the functional and three dimensional structural unit of a polypeptide

So, the secondary structure is formed of combining of

a-helix, b-sheet to form

a motif Motifs combine to form

a domain

Secondary structure (cont.)

Tertiary structure

Definition:

Refers to folding of domains and the final arrangement of domains in a polypeptide Polypeptide chains more than 200 amino acids in length generally consists at least two domains

Tertiary structure is stabilized by:

1- Disulfide bonds: between –SH groups of two cysteine amino acids 2- Hydrophobic interactions: between amino acids with nonpolar side chains 3- Hydrogen bonds4- Ionic interactions: between COO- of aspartate or glutamate with –NH3+ of lysine

bonds stabilizing tertiary structure

A protein structure with primary, secondary

& tertiary levels of structure

Primary structure (amino acid sequence ) Secondary structure (coiling) Tertiary structure (folding)

Quaternary structure

Definition:The arrangements of more than one polypeptide subunit in a protein is called

quaternary structure of protein

Monomeric proteins:

Proteins consists of only one polypeptide chain (subunit) (as for example myoglobin)

Polymeric proteins (dimeric, trimeric or tetrameric, etc):

Proteins contain more than one polypeptide chain (subunits)(as for example hemoglobin which is tetrameric)

• Subunits are held together by noncovalent interactions (as hydrogen, ionic bonds)

• Subunits may work cooperatively with each other (as in hemoglobin) or work independently of each other.

Some important properties of proteins

1- Solubility of proteins in water:

• Most proteins are soluble in water and insoluble in nonpolar fat solvents.• Scleroproteins are insoluble in water.

2- Amphoteric properties of proteins:

• Proteins contain free carboxyl and amino groups at the ends of the peptide chains. This makes proteins react with acids and alkalies (i.e. amphoteric)

• Each protein has its own isoelectric point which is the pH at which it carries equal positive and negative charge.(neutral)

On the acid side of the isoelectric point (lower pH), proteins carries positive

charge while on the alkaline side (higher pH) they carry negative charge.

3- Denaturation of proteins:

is the destruction of the secondary and tertiary structures of protein molecule without loss of the primary structure (peptide bonds).

Effects of denaturation of proteins:

1-Loss of biological activities of proteins2- Permanent disorder (irreversible) in common cases (reversible in rare cases).

Denaturation can be produced by: 1-Physical agents as heat, ultaviolet rays, X rays… etc2-Chemical agents: as strong acids, alkalies, heavy metals

N.B. Protreolytic enzymes (e.g. enzymes of digestion) hydrolyse the polypeptide chain (destruct peptide bond leading to loss of the primary .level of protein structure). This is different from denaturation.

Some important properties of proteins

Classification of proteins

1- Simple proteins on hydrolysis, simple proteins yield amino acids only.

2- Conjugated proteins

On hydrolysis they yield amino acids & a non protein part (prosthetic group)

3- Derived proteins They are decomposition products of proteins

On hydrolysis, simple proteins yield amino acids only.

Albumin & globulins- available in milk and egg (of high nutritional value)- In blood they are two of the plasma proteins.

Histones- a basic protein as it is rich in histidine. - available with nucleic acids in chromosomes and in the globin part of hemoglobin.

ScleroproteinsThey are the most resistant proteins. They form the protective and supportive proteins of the body include: 1-Collagen in tendons, cartilage, bones and connective tissue. 2- Elastin in elastic fibers in lung and big arteries 3- Reticulin in reticular connective tissues of liver, spleen and kidney 4- Keratin in hair, nails and skin

Simple proteins (examples)

These proteins on hydrolysis give amino acids and non protein parts called the prosthetic groups

Phosphoproteins Proteins that are combinedwith phosphoric acid Example: caseinogen of milk

Glycoprotein They consists of proteins + mucopolysaccharides (carbohydrates) They occur in mucous secretions, cartilage, bone & connective tissues. Examples: Cholndroitin sulphate, Mucoitin sulphate & heparin

Chromoproteins As hemoglobin in blood and myoglobin of muscles Hemoglobin & myoglobin are composed of protein part (globin) & non protein part (heme).

Lipoproteins Lipoproteins are conjugated proteins containing proteins & lipids. Plasma lipoproteins transport lipids in blood.

Nucleoproteins They are composed of basic proteins as histones and nucleic acid (DNA of chromosomes).

Conjugated proteins (examples)