AMINO ACIDS

 Proteins are organic compounds with a high molecular weight.

 Twenty different amino acids found in protein structure.
 All are α-amino acids except proline and hydroxyproline are imino acid.
 Basic structure of amino acid:

a a
R – CH – COOH R – CH – COO-
NH2 NH3+
General formula of a-amino acids Ionizable form at physiological pH

Classification of Amino Acids

I - Chemical classification

Chemical Classification of
Amino Acids

Aliphatic Aromatic Heterocyclic

Amino Acids Amino Acids Amino Acids
Phenylalanine Histidine
Tyrosine Proline
Tryptophan Hydroxyproline

Neutral aliphatic Acidic aliphatic Basic aliphatic

Amino Acids Amino Acids Amino Acids
Glycine Aspartic acid Lysine
Alanine Glutamic acid Hydroxylysine
Valine Arginine
Leucine Branched chain amino acids
Isoleucine
Serine
Threonine Hydroxy amino acids
Cysteine
Sulfur containing amino acids
Methionine
Asparagine
Amides of acidic amino acids
Glutamine

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Aliphatic amino acids:
1- Neutral amino acids: Glycine and alanine
Short chain amino acids
Branched amino acids Valine, leucine, isoleucine
Hydroxyl containing amino Serine and thereonine
acids
Sulfur containing amino Cysteine (contain thiol group SH)
acids Cystine (formed of two cysteine linked by
disulfide bond)
methionine
Amide amino acids Asparagine and glutamine
2- Acidic amino acids Aspartic and Glutamic acids
3- Basic amino acids Arginine, lysine, hydroxylysine
Histidine ( heterocyclic basic)
Aromatic amino acids Phenylalanine
Tyrosine ( aromatic hydroxyl containing
amino acid)
Tryptophan (heterocyclic)
Heterocyclic amino acids Histidine
Tryptophan (heterocyclic aromatic)
Proline and hydroxyproline (Imino acids)

A- Amino Acids with Aliphatic Side Chain

I - Aliphatic neutral amino acids :
1- Glycine (Gly or G) 2- Alanine (Ala or A)

HCH – COOH CH3 – CH – COOH

NH2 NH2

The three branched chain amino acids.

3- Valine (Val or V) 4- Leucine (Leu or L)

CH3 CH3
CH – CH – COOH CH – CH2 – CH – COOH
CH3 CH3
NH2 NH2

5- Isoleucine (Ile or I)
CH3 – CH2
CH – CH – COOH
CH3
NH2

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B- Amino acids aliphatic contain OH group at their side chain

1- Serine (Ser or S) 2- Threonine (Thr or T)

CH2 – CH – COOH CH3 – CH – CH – COOH
OH NH2 OH NH2

C- Amino acids aliphatic contain sulfur.

1- Cysteine (Cys or C) 2- Cystine

Two cysteine are conjugated by
disulfide bond by removal of two
hydrogen atoms.
CH2 – CH – COOH CH2 – CH – COOH
SH NH2 S NH2
S NH2
CH2 – CH – COOH
3- Methionine (Met or M)
CH2 – CH2 – CH – COOH
S-CH3 NH2

D- Amino acids with acidic or amide group :

1- Aspartic acid (Asp or D) 2- Asparagine (Asn or N)

CH2 – COOH NH3 H2 O CH2 – CO– NH2

H2N – CH – COOH H2N – CH – COOH

3- Glutamic acid (Glu or E) 4- Glutamine (Gln or Q)

CH2 – COOH NH3 H2 O CH2 – CO– NH2

CH2 CH2
H2N – CH – COOH H2N – CH – COOH

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E- Amino acids with basic side chain :

1- Lysine (Lys or K) e
CH2 – CH2 – CH2 – CH2 – CH – COOH
NH2
NH2
2- Hydroxylysine e
CH2 – CH2 – CH2 – CH2 – CH – COOH

NH2 NH2
OH

3- Histidine (His or H) (contain imidazole ring)

CH2 – CH – COOH

N NH NH2
4- Arginine (Arg or R)

NH2
HN = C d g  a
NH – CH2 – CH2 – CH2 – CH – COOH
NH2

F- Amino Acids with Side Chains Containing Aromatic Rings:

1- Phenylalanine (Phe or F) 2- Tyrosine (Tyr or

Y)(contain also OH)

CH2 – CH – COOH CH2 – CH – COOH

NH2 NH2

OH

CH2 – CH – COOH
3- Tryptophan (Trp or W)
(Contain indole ring) NH2
N
H

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G- Imino acids. (contain pyrolidine ring)

Proline (Pro or P) Hydroxyproline

4 3
HO 4 3
5 2 5 2
1 COOH 1 COOH
N N
H H
N.B: hydroxyproline and hydroxylysine are formed from proline and lysine by
hydroxylation
N.B: selelnocysteine is the 21st amino acid, it is formed by replacement of
sulfur (S) by selenium (Se)
N.B: Heterocyclic amino acids:
These are amino acids which contain heterocyclic ring other than phenyl ring:
Histidine, tryptophan, proline and hydroxyproline
N.B: Tyrosine is aromatic hydroxyl containing amino acid

II. Classification of Amino Acids According to” Polarity” of Side Chain

(R)
1- amino acids with polar charged R groups:
A- Basic amino acids (positively charged) (diamino monocarboxylic): Lysine,
Hydroxylysine, Arginine, Histidine
B- Acidic amino acids (negatively charged) (dicarboxylic monoamino):
Aspartic, Glutamic acids
3- Amino acids with Polar uncharged R groups:
 They contain polar group that forms hydrogen bond with water.
 They include:
- Hydroxy amino acids: serine, threonine, tyrosine & hydroxyproline.
- SH group containing amino acids: cystiene
- Amide group containing amino acids: Asparagine and glutamine
3-Non polar none charged( amino acids with uncharged R groups)
-The rest of amino acids: glycine, alanine, valine, leucine, isoleucine,
methionine, phenylalanine, tryptophan and proline.
III. Nutritional classification of amino acids
1- Essential amino acids:
 They are not formed in body, so it is essential to take them in diet
 Their deficiency decreases the rate of growth and protein synthesis (-ve
nitrogen balance)
 They include : VIPTLMH
- Threonine (OH), Methinonine (S)
- Histidine (Heterocyclic basic), lysine. (Basic)
- Valine , Leucine , Isoleucine. (Branched)
- Phenylalanine (aromatic), Tryptophan (aromatic and heterocyclic)

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2- Semi (= half)-essential amino acids:
 They are formed in the body at rate enough for adults but not for growing
animals
 They include: Arginine.

3-Non essential amino acids:

 They are formed in the body at a rate enough for adults and growing
animals.
 They include the rest of amino acids.

High biological value protein Low biological value protein

they contain all essential amino acids : they are deficient in one or more of
essential amino acids
e.g: milk & egg protein. e.g: Zein of maize (deficient in
tryptophan)

IV - Metabolic Classification of Amino Acids

According to their metabolic fate, amino acids can be classified into 3 main
groups:
1 – Pure glucogenic amino acids :
 Amino acids give glucose inside the body and include all amino acids
except the members of the other two groups.
2 – Pure ketogenic amino acids :
 Amino acids give ketone bodies inside the body and include leucine and
lysine.
3 - Glucogenic and ketogenic (mixed) amino acids:
 Amino acids give glucose and ketone bodies inside the body and include
phenylalanine, tyrosine, tryptophan and isoleucine.
Properties of amino acids
I- Amphoteric properties
 Amino acids can react with acids or bases, so they are ampholytes.
 In acidic medium they carry positive charge (R-NH3+).
 In alkaline medium they carry negative charge (R-COO-)
 Iso electric point: (IEP): amino acids form dipolar ions= zwitterions
(carry both positive & negative) at pH 6.02 for all monocarboxylic-
monoamino acids, in this form amino acids can’t migrate in the electric
field
 So, amino acids are present in three forms according to the pH of the
solution and the uncharged form is not present at any pH.

HCl R – CH – COO- NaOH R – CH – COO- Na+

R – CH – COOH
NH3+Cl- NH3+ NH2 + H2O
Acidic medium Zwitterion (IEP) Alkaline medium

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 2- Peptide bond formation
 Condensation of COOH (carboxyl group) of one amino acid with NH2
(amino group) of second amino acid to form peptide bond
R1 R2 R1 R2
H2 O
NH2 – CH - COOH + NH2 – CH - COOH NH2 – CH - CO NH – CH - COOH
Dipeptide
2 amino acids form dipeptide, 3 amino acids form tripeptide

PROTEINS OF BIOLOGICAL IMPORTANCE

 Oligopeptides: 2-10 amino acids.
 Polypeptides: 11-49 amino acids.
 Proteins: more than 50 with molecular weight more than 5000

the biological importance of proteins:

1- Provide the body with essential amino acids, nitrogen and sulfur.
2- Enzymes are mainly protein in nature.
3- Many hormones are peptides or protein in nature (e.g. glucagon and insulin).
4- The antibodies (immunoglobulins) are proteins.
5- Hemoglobin is a chromoprotein. It carries O2 from the lung to tissues.
6- Plasma proteins are responsible for most effective osmotic pressure of the
blood.
7- Plasma proteins help the transport of many substances in the blood e.g. lipids
forming lipoprotein complexes, hormones (e.g. thyroid hormones) and minerals
(e.g. calcium, iron and copper).
8- They form very important components of different types of cell membranes
e.g. receptors and transporters.

Structure of Proteins

Different Levels of Protein Structure

- Proteins in their native state are characterized by their three dimensional
structure.
- Proteins with one polypeptide chain have primary, secondary and tertiary
structures.
- Proteins with two or more polypeptide chains have an additional quaternary
structure.
Structure of proteins can be divided into four orders:
I- Primary Structure:
 It is the sequence of amino acids.
 Amino acids are joined together by peptide bonds.
 Primary structure is maintained (stabilized) by peptide bond.
 Amino acid sequence is specific for each protein.

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  Each polypeptide chain has:
- A left end, with free terminal amino group (N-terminus)(the first amino
acid).
- A right end free terminal carboxyl group (C-terminus)(the last amino
acid).
 Synthesis of polypeptide chain starts from N-terminus towards C-
terminus.
 Change of one amino acid leads to physiological effect.
 The genetic information in DNA controls the primary structure of protein.
 Primary structure of protein determines the secondary & tertiary structure.

II- Secondary Structure:

 Two regular forms: α-helical or β-pleated sheets.
 Other forms: loop regions, β bends and disordered regions.
1. a-Helix
- Folding of the polypeptide chain, along its long axis, into specific coiled
structure.
- Held together by hydrogen bonds.
Main features of a-helix
1. The chain is coiled around long axis to form right handed helix
2. The a-helix is stabilized by intra-chain hydrogen bonds, which are formed
between NH groups and C=O groups.
3. Each peptide bond participates in the hydrogen bonding. This gives
maximum stability to a-helix.
4. The R-groups (side chain) of amino acids project outwards of the helix.
5. The R groups of some amino acids can disrupt the a-helical structure e.g.
proline, tryptophan, histidine, lysine, arginine, aspartic acid and glutamic
acid, due to:
- Formation of other types of bonds as ionic bonds
- Or their ring structures disturb the helical formation.
2. β -Pleated Sheet
Main features of β-pleated sheet
 It is formed between 2-5 fully extended polypeptide chains.
 The R-groups (side chain) are above or below the plane of the sheet.
 The β -pleated sheet is stabilized by inter chain hydrogen bonds.
 Parallel β-pleated sheet: the adjacent polypeptide chains run in same
direction (N to C terminus).
 Anti-parallel β-pleated sheet: the adjacent polypeptide chains run in
opposite direction.
N.B.
- β-pleated sheets may form between different regions of the same polypeptide
chain by intra-chain hydrogen bond

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- An individual protein may contain both types of secondary structure. Some
proteins, like collagen, contain neither but have their own more characteristic
secondary structures.

III- Tertiary Structure:

- Folding of the polypeptide chain into three dimensional structure.
- Maintained by different types of bonds or interactions as follows:
1- Hydrophobic interactions between nonpolar side chains of amino
acids.
2- Ionic bonds (salt bridges) between NH3+ of basic A.A & COO- of
acidic amino acids.
3- Hydrogen bonds between polar side chains of amino acids.
4- Van der waals interactions: weak interactions.
5- Disulfide bonds between two cysteine are connected to form cystine
as in keratin & insulin.

IV- Quaternary structure:

- Only in certain types of proteins which have two or more polypeptide chains
(several subunits or polymers).
- Each subunit has its own primary, secondary and tertiary structure and the
subunits combine forming the quaternary structure.
- May be essential for the activity of certain proteins e.g. enzymes and
hemoglobin.
- Stabilized by: hydrogen bonding, electrostatic interactions, hydrophobic
interactions, Van der Waals interactions and disulfide bonds.
Chaperones:
 They are group of molecular proteins that promote efficient protein
folding and prevent its aggregation.
 Age related defect in action of chaperons may lead to some diseases as
Alzheimer and Parkinson's disease.

Denaturation of Proteins
 Denaturation is a specific property of proteins.
 Carbohydrates and lipids cannot be denatured.
 Denaturation is the change of the natural state "Native state" of proteins.
 It is due to the rupture of chemical bonds that stabilize the secondary,
tertiary and quaternary structure of the protein.
 The only bond not destroyed is: peptide bond
 The only structure not destroyed is: primary structure
 It may be reversible or irreversible and may result in protein coagulation
e.g. albumin coagulation by heat (due to formation of disulfide cross
linkage).

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Factors that produce denaturation :
1- Physical agents:
As heat, mechanical agitation, sonication, ultraviolet irradiation, X-ray etc....
2 - Chemical agents:
As acids, alkalis, alcohols, urea, salts of heavy metals like Pb2+, Ag2+, Cu2+etc....
Effects of denaturation on proteins:
1 - Loss of the secondary, tertiary and quaternary structure of proteins.
2 - Increased viscosity.
3 - Decreased solubility due to exposure of nonpolar hydrophobic groups.
4 - Increased digestibility by proteolytic enzymes due to exposure of peptide
bonds.
5 - Loss of biologic activity e.g. inactivation of enzymes.
6 - Loss of antigenic property i.e. injection of denatured protein cannot induce
antibody formation within the body
Classification of Proteins
Conformational Classification:
Fibrous protein Globular protein
Parallel long fibers Spherical
Collagen, elastin, keratin Enzymes, hemoglobin, myoglobin,
hormones, immunoglobulins and
plasma proteins.

Protein Synthesis and Degradation

Protein synthesis (translation):

- Proteins are synthesized either on:
 Free ribosomes or on
 Ribosomes bound to ER.
Protein degradation:
 The half-life of the protein is determined by the amino acid composition of
the protein especially the amino- terminus residues.
 All proteins are degraded eventually by cell’s proteolytic system.
- The two systems for protein degradation are the:

Lysosomal protein degradation proteosomal degradation pathway

pathway
It degrades long half-life proteins It degrades proteins with shorter half-
lives or abnormal proteins
It is ATP dependent and use enzymes
that add ubiquitin to protein targeted
for degradation

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