PROTEIN CHEMISTRY - I

By Dr ANURAG YADAVModerator Dr ARUN KUMAR K

Content :

Definition of amino acids

Definition of peptide bond

General structure of amino acids

Numbering of amino acids

Nomenclature of amino acids.

Classification of amino acids.

Properties of amino acids.

Biological importance of amino acid

derivatives.

OVERVIEW:

Proteins are most abundant & functionally

diverse molecule in living system.

Virtually every life process

depends on this class of molecules.

Enzymes & polypeptide hormones direct &

regulate body metabolism.

In bone, protein collagen forms a frame work

for deposition of salts.

Immunoglobulin's fight against infectious

bacteria & viruses

DEFINITION Amino acids are group of organic compounds

containing two functional groups – amino and carboxyl.

PEPTIDE BOND

Is chemical bond formed between the α-carboxyl groups and α-amino group of next amino acid.

It’s the primary linkage of all protein structures.

NON STANDARD AMINO ACIDS:

Amino acids can b classed as standard amino acids and non standard amino acids.

Of 300 amino acids human body codes 20 amino acids.

These although never incorporated into structure of protein , but play several biological role.

These include :

D-amino acids: bact cell wall, antibiotics

Non-protein amino acids: taurine,homocysteine.etc.,

Amino acid derivatives: GABA, DOPA, hydroxy proline & hydroxy lysine.

AMINO ACIDS

They are monomer unit of proteins

All major structural and functional aspect of body

are carried out by the proteins

20 amino acids are seen in humans.

Most of amino acids are in α-amino acids except

proline

General structure

NUMBERING OF AMINO ACID:

ABBREVIATIONS & SYMBOLS FOR AMINO ACIDS

a) Unique letters first: if only one amino acid begins with particular letter , than letter is used as symbol.(I=Isoleucine).

b) Most commonly occurring Amino Acid have priority if more than one amino acid begin with particular letter & it receive that letter as symbol (Glycine>Glutamate; so G=Glycine.

c) Similar sounding names : F-Phenylalanine.W-tryptophan.

d) Letter close to initial letter: is assigned as symbol which is close to first letter as close .

Eg: k- lysine

CLASSIFICATION OF AMINO ACIDS:

Based on structure

Based on side chain

Based on metabolic fate

Based on nutritional requirement

BASED ON STRUCTURE:

Aliphatic amino acids.

Aromatic amino acids.

Heterocyclic amino acids.

Imino acids.

Derived amino acids.

ALIPHATIC AMINO ACIDS:

Monoamino monocarboxylic acids

Monoamino dicarboxylic acids

Dibasic monocarboxylic acids

Simple amino acid: Glycine. Alanine.

Branched chain amino acids: Valine. Leucine. Isoleucine.

Hydroxyamino acids: Serine.

Threonine.

Sulfur containing amino acids: Cysteine.

methionine.

Amino acid with Amide group: Glutamine. Asparagine.

Monoamino dicarboxylic acids: Aspartic acid. Glutamic acid.

Dibasic monocarboxylic acids: Lysine. Arginine.

AROMATIC AMINO ACIDS:

Phenylalanine, Tyrosine.

HETEROCYCLIC AMINO ACIDS:

Tryptophan

Histidine

IMINO ACID: Proline.

Tryptophan(Trp)(W) with indole group

Derived amino acids :

• Derived amino acid found in proteins:

Hydroxyproline

• Derived amino acid not found in proteins:

Ornithine and citrulline.

• Non alpha amino acids: GABA, βalanine.

SPECIAL GROUPS IN AMINO ACIDS:

Arginine Guanidinium group

Phenylalanine Benzene group

Tyrosine Phenol group

Tryptophan Indole group

Histidine Imidazole group

Proline Pyrrolidine group

BASED ON SIDE CHAIN:

Amino acids having Non-polar side chain:

Has an Non-polar side chain that doesnot gain/lose proton/particiate in hydrogen/ionic bond.

They are usually hydrophobic.

LOCATION: The side chain tends to cluster

together in interior of protein & this phenomenon is called as hydrophobic effect.

Eg: Alanine, Valine, Leucine, Isoleucine, Proline, Phenylalanine, Tryptophan.

Amino acids with uncharged/Non-ionic polar:

These are with ZERO net charge at neutral pH .

These amino acids are hydrophilic. eg: Glycine, Serine, Threonine & Asparagine.

Amino acids having charged/Ionic polar side chain:

a)Acidic amino acid: they are negatively charge on R group. Eg: Aspartic acid.

Glutamic acid.

b) Basic amino acids: they have positive charge on R group. Eg: Lysine.

Argenine. Histidine.

BASED ON METABOLIC FATE:

a) Purely ketogenic: converted to ketone bodies (fat can be synthesized from these amino acids). Eg:Leucine

b) Both ketogenic & glucogenic: Lysine, isoleucine, Phenylalanine, Tyrosine, Tryptophan are partially ketogenic & glucogenic.

c) Purely glucogenic: all remaining 14 amino acids are glucogenic as they enter only into the glucogenic pathway.

BASED ON NUTRITIONAL REQUIREMENT:

Essential/indispensable

Cannot be synthesized by

the body.

Needed to be supplied in

diet.

Phenylalanine, Valine,

Threonine, Trptophan,

lsoleucine, Methionine,

Leusine, Lysine

Non-essential

they can be synthesized

by body & need not to be

supplemented.

Alanine, Aspargine,

Aspartate, Glutamate,

Glutamine, Tyrosine,

Serine, Proline, Glycine,

Cysteine.

Semi-essential amino acids: they are synthesized

by the adults , but the growing children need to be

supplemented in food . They

are :Arginine Histidine.

Conditional essential amino acids: when person

suffers from chronic illness he lose ability to

manufacture enough Non-essential amino acids &

hence need to be supplemented.

- Arginine, Glycine, Cysteine, Tyrosine, Proline,

Glutamine & Taurine.

SELENOCYSTEINE- 21ST AMINO ACID

21st amino acid

Derivative of serine

Structure similar to cysteine,

but with an atom of

selenium(SeH) taking place of

sulphadryl (SH).

Stop codon: UGA

It’s present in active site of

several enzymes like

glutathione peroxidase.

PYRROLYSINE:

22nd amino acid.

• lysine derivative

encoded by UAG codon

• Used by some

prokaryotes.

• Present in methyl

transferase enzyme of

bacteria.

PROPERTIES OF AMINO ACIDS:

Physical properties :

They are colourless.

Taste varies( glycine-sweet, leucine-tasteless,

arginine-bitter).

Soluble in water .

Melting point is higher >200°c.

Optical activity.

Ampholyte & Isoelectric point.

OPTICAL ACTIVITY:

All amino acids have

asymmetric carbon atom

hence show optical

isomers.

Except glycine.

The mirror image are

produced with reference

to α-carbon atom as D &

L isomers.

D & L ISOMERS

L amino acid occur in nature & therefore called as Natural amino acid

D-amino acids are found in antibiotics & bacterial cell wall.

AMPHOTERIC NATURE & ISOELECTRIC POINT

At physiological pH amino acids exists as ions.

They act as ampholyte/ zwitter ion in solution

depending on pH of the medium.

In acidic medium acts as cations & in alkaline

medium as anion.

All groups are ionized but cancel eachother

At this particular pH the molecule carry no net charge is known as Isolectric point & these are called zwitter ions.

hence there will be no mobility in an electrical field.

Solubility & buffering capacity will be minimum.

TITRATION CURVE FOR AMINO ACID

pI= pK1 + pK2

2

In case of amino acid having more than two

ionizable groups, correspondingly there will

be more pK values , eg: aspartic acid

Features of a molecule at iso-electric

point:

molecule minimally soluble & maximally

precipitated.

Viscosity of substance is minimum.

Buffering capacity is at its minimum.

The conductivity & osmotic pressure are at

minimum.

Molecule is electrically neutral.

CHEMICAL REACTIONS

Due to carboxyl group:1. amino acids form salts (COONa) with bases

& ester (-COOR’ ) with alcohol.

2. Decarboxylation: form corresponding amine.

1. Histidine histamine + CO2

2. Tyrosine tyramine + CO2

3. Tryptophan tryptamine + CO2

4. Lysine cadaverine + CO2

5. Glutamic acid GABA + CO2

Reactions with ammonia: the carboxyl

group of dicarboxylic AA other than α-

carboxyl combine with ammonia to form

corresponding amide.

Aspartic acid +NH3 =

Asparagine. glutamic acid +NH3=

Glutamine.

REACTIONS DUE TO AMINO GROUP:

Transamination : α-amino group transferred to α-keto acid to form new amino acid & α-keto acid.

Oxidative deamination: removal of α-amino group to form α-keto acids and ammonia.

Formation of carbamino compound: in

alkaline pH CO2 adds to α-amino group to

form carbamino compound. It serves

transport of CO2 by hemoglobin.

Hb-NH2 Hb-NH-COOH

REACTIONS DUE TO SIDE CHAIN:

Transmethylation: the methyl group is transferrred;

Eg: methionine + acceptor methylated acceptor

+ homocysteine.

Ester formation by OH group:

Serine(OH)+Phosphoric acid Phosphoproteins

and also forms glycoproteins.

Reactions of amide group: glycoprotein is

formed when amide group of Glutamine &

Asparagine forms N-glycosidic bonds with

carbohydrate.

Reaction of SH group: cysteine has a sulfhydryl

group it can form disulfide bond with another

residue. Can also connect two polypeptide

chains forming interchain disulfide bonds.

COLOR REACTIONS OF AMINO ACIDS & PROTEINS

1.Ninhydrin Alpha amino group

2.Biuret reaction Peptide bonds

3.Xanthoproteic test Benzene ring(Phe,Tyr,Trp)

4.Millon’s test Phenol(Tyrosine)

5.Aldehyde test Indole(Tryptophan)

6.Sakaguchi’s test Guanidinium(Arginine)

7.Sulfur test Sulfhydryl(Cysteine)

8.Nitroprusside test Sulfhydryl(Cysteine)

9.Pauly’s test Imidazole(Histidine)

AMINO ACID DERIVATIVES OF IMPORTANCE

GABA: Derivative of glutamic acid & dopamine. A neurotransmitter GABA pentin can pass BBB & form GABA in

brain.

Hitamine: Synthesized from histidine. Mediator in allergic reactions.

Thyroxine: From tyrosine. An thyroid hormone.

Cycloserine: Derivative of serine As an antituberculous drug

Histidine: Important in buffering.

Ornithine: & citrulline are derivative of arginine, essential for

urea synthesis.

REFERENCES:

Text book of biochemistry- DM Vasudevan. Lippincott’s illustrated biochemistry. Biochemistry – U Satyanarayana.

Thank you