chemistry of amino acids

Biochemistry For Medics 1

Chemistry of amino acids

Biochemistry for medicswww.namrata.co

7/5/2012

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Amino acidsProvide the monomer units from which the long polypeptide chains of proteins are synthesized L-amino acids and their derivatives participate in cellular functions as diverse as nerve transmission and the biosynthesis of porphyrins, purines, pyrimidines, and urea. Short polymers of amino acids called peptides perform prominent roles in the neuroendocrine system as hormones, hormone-releasing factors, neuromodulators, or neurotransmitters.

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General structure of an amino acid

Each amino acid (except proline) has a carboxyl group, an amino group and a distinctive side chain bonded to the alpha carbon atom. At physiological pH the carboxyl group is dissociated forming the negatively charged carboxylate ion(-COO-), and the amino group is protonated(-NH3

+)

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Classification of amino acids

Amino acids can be classified in 4 ways:1. Based on structure2. Based on the side chain characters3. Based on nutritional requirements4. Based on metabolic fate

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They are classified in three broad categories: Mono amino mono carboxylic acidIt is further subdivided in 5 groups:a. Simple amino acids-example: glycine, alanineb. Branched chain amino acids-eg: valine,leucine,isoleucinec. Hydroxyl group containing amino acids-eg: serine, threonined. Sulphur containing amino acids-eg: cysteine,cystine,methioninee. Amide group containing amino acids-e.g.-

asparagine,glutamine

Mono amino dicarboxylic acidExample :aspartic acid, glutamic acid

Di /poly amino mono carboxylic acidExample : lysine,arginine

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1)Classification based on structure



I. Aliphatic Amino Acids:a) Mono-amino mono-carboxylic acids:

Simple amino acids: Glycine , Alanine

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I. Aliphatic Amino Acids:

a) Mono-amino mono-carboxylic acids:Branched chain amino acids: Valine, Leucine and Isoleucine

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I. Aliphatic Amino Acids:a) Mono-amino mono-carboxylic acids:-OH group-containing amino acids: Serine and Threonine

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I. Aliphatic Amino Acids:a) Mono-amino mono-carboxylic acids:Sulfur-containing amino acids: Cysteine, Cystine(Formed by linking of two cysteine residues) and Methionine.

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I. Aliphatic Amino Acids:a) Mono-amino mono-carboxylic acids:

Amide group-containing amino acids:Glutamine and Asparagine

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I. Aliphatic Amino Acids:a) Mono-amino di-carboxylic acids: Aspartic

acid and Glutamic acid

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I. Aliphatic Amino Acids:a) Di- basic mono-carboxylic acids:

Arginine and Lysine

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1) Classification based on structure

ii ) Aromatic amino acids- Phenyl alanine and tyrosine

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iii) Heterocyclic Amino Acids: Tryptophan and Histidine

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iv) Imino acid- Proline

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V. Derived Amino Acids: Non-α-amino acids

e.g.: β-alanine, γ-amino butyric acid (GABA), δ-amino Levulinic acid

Derived and Incorporated in tissue proteins:e.g.: Hydroxy-proline, hydroxy-lysine

Derived but not incorporated in tissue proteins:e.g.: Ornithine, Citrulline, Homocysteine, Argino succinic acid

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2) Classification based on side chain characters

A. Amino acids with a non-polar side-chain:e.g.: Alanine, Valine, Leucine, Isoleucine,

Phenylalanine, Tryptophan, Proline

Each of these amino acids has a side chain that does not bind or give off protons or participates in hydrogen or ionic bonds.

Side chains of these amino acids can be thought of as “Oily” or lipid like, a property that promotes hydrophobic interactions.

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Biochemistry For Medics 187/5/2012

Amino acids with a non-polar side-chain:


2) Classification based on side chain characters

B) Amino acids with a polar but uncharged side-chain:e.g. Serine, Threonine, Tyrosine, Cysteine, Asparagine and Glutamine.

These amino acids are uncharged at neutral pH,although the side chains of cysteine and Tyrosinecan lose a proton at an alkaline pH.Serine , Threonine and Tyrosine each contains a polar hydroxyl group that can participate in hydrogen bond formation. Side chains of Asparagine and Glutamine contain a carbonyl group and amide group, they can also

participate in hydrogen bond formation.

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Amino acids with a polar but uncharged side-chain


2) Classification based on side chain charactersC) Amino acids with a charged side-chain

a) Amino acids with a positively charged side-chain:The basic amino acids- Lysine, Arginine and Histidine

b) Amino acids with a negatively charged side-chain:The acidic amino acids- Glutamic acid and Aspartic acid

They are hydrophilic in nature.

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Amino acids with a charged side-chain


3)- Classification based on nutritional requirementsI. Essential amino acids:

These amino acids cannot be synthesized in the body and have to be present essentially in the diet. Examples-Valine, Isoleucine, Leucine, Lysine, Methionine, Threonine, Tryptophan and Phenylalanine.

II. Semi-essential amino acids:These amino acids can be synthesized in the body but the rate of synthesis is lesser than the requirement(e.g. during growth, repair or pregnancy) Examples-Arginine and Histidine.

III. Non-essential amino acids:These amino acids are synthesized in the body, thus their absence in the diet does not adversely affect the growth.Examples- Glycine, Alanine, and the other remaining amino acids.

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4)-Classification based on metabolic fate

The carbon skeleton of amino acids can be used either for glucose production or for the production of ketone bodies, Based on that I. Both glucogenic and ketogenic amino acids:

Isoleucine, Tyrosine, Phenylalanine and Tryptophan

II. Purely Ketogenic amino acids: Leucine and Lysine

III. Purely Glucogenic amino acids:The remaining 14 amino acids are glucogenic. Alanine, valine ,serine, threonine, glycine, methionine, asparagine, glutamine, cysteine, cystine, aspartic acid, glutamic acid, histidine and arginine.

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Non standard amino acidsOf the over 300 naturally occurring amino acids, 20 constitute the monomer units of proteins. These 20 amino acids are called the Primary or Standard amino acids.Seleno cysteine is the 21st Amino AcidThe other are Pyroglutamate and Pyrolysine.

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Naming of Amino acids

Each amino acid has three letter (code) and one letter (Symbol) abbreviations- Examples-1) Unique first letterCysteine- Cys- CHistidine- His- H2) Priority of commonly occurring amino acidsAlanine- Ala- A (Preference over Aspartate) Glycine- Gly-G (Preference over Glutamate)

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Naming of Amino acids

3) Similar sounding names- Some one letter symbols sound like the amino acids they represent- Example Tryptophan – W (Twyptophan) Phenyl alanine – F4) Letters close to initial letterAspartate- Asx- B( near A)Lysine Lys- K(near L)

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Amino acid abbreviations


Special groups in amino acids

Arginine- Guanidinium groupPhenyl Alanine- Benzene group Tyrosine- Phenol groupTryptophan- Indole group Histidine- Imidazole groupProline- Pyrrolidine Proline has a secondary amino group, hence it is an imino acid.

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Properties of amino acids

Physical properties-ColorlessCrystallineMay be sweet(Glycine, Alanine, Valine), tasteless(Leucine) or bitter(Arginine, Isoleucine). Aspartame- An artificial sweetener contains Aspartic acid and Phenyl alanine.Soluble in water, acids, alkalis but insoluble in organic solventsHigh melting point(More than 2000c)

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Isoelectric point

Amino acids can exist as ampholytes or zwitterions in solution, depending upon pH of the medium.The pH at which the amino acids exist as zwitterions, with no net charge on them is called Isoelectric pH or Isoelectric point.In acidic medium, the amino acids exist as cationsIn alkaline medium , they exist as anions.

Due to no net charge, there is no electrophoretic mobility at Isoelectric pH.Solubility and buffering capacity are also minimum at Isoelectric pH7/5/2012


Isoelectric point

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Titration of amino acidsIf HCl is added drop wise to am amino acid solution, at a particular p H, 50 % of the molecules are in the cationic form and 50% are in the zwitterion form. This pH is pK1(with regard to COOH)If the titration is done from the Isoelectric point with NaOH, molecules acquire the anionic form. When 50 % of the molecules are in the anionic form and 50% are in the zwitterion form. This pH is pK2(with regard to NH2)

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Titration of Glycine

For mono amino mono carboxylic amino acids-pI = pK1+pK2 -------------

2

The buffering action is maximum in and around pK1or at pK2 but is minimum at pI

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pKa of some amino acids


Optical properties of amino acids

The α carbon of each amino acid is attached to four different groups and is thus a chiral or optically active carbon atom.Glycine is exceptional because there are two hydrogen substituents at the α carbon, thus it is optically inactive.Amino acids with asymmetric centre at the α carbon can exist in two forms, D and L forms that are mirror images of each other and are called Enantiomers.All amino acids found in proteins are of L- configurationD- amino acids are found in some antibiotics and in bacterial cell walls.

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L & D isomers of amino acids


Reactions of amino acids

1) Reactions due to amino group2) Reactions due to carboxyl group 3) Reactions due to side chain4) Reaction due to both amino and

carboxyl groups

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Reactions due to amino groupOxidative deamination-α amino group is

removed and corresponding α-keto acid is formed. α-keto acid produced is either converted to glucose or ketone bodies or is completely oxidized.

Transamination-Transfer of an α amino group from an amino acid to an α keto acid to form a new amino acid and a corresponding keto acid.

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Reactions due to amino group

Formation of carbamino compoundCO2 binds to α amino acid on the globin chain of hemoglobin to form carbamino hemoglobinThe reaction takes place at alkaline pH and serves as a mechanism for the transfer of Carbon dioxide from the tissues to the lungs by hemoglobin.

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Reactions due to carboxyl group

1) Decarboxylation- Amino acids undergo alpha decarboxylation to form corresponding amines. Examples-

Glutamic acid GABA Histidine Histamine

Tyrosine Tyramine

2) Formation of amide linkage• Non α carboxyl group of an acidic amino acid

reacts with ammonia by condensation reaction to form corresponding amides

Aspartic acid Asparagine Glutamic acid Glutamine

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Reactions due to side chains 1) Ester formation OH containing amino acids e.g. serine,

threonine can form esters with phosphoric acid in the formation of phosphoproteins.

OH group containing amino acid can also form: Glycosides – by forming

O- glycosidic bond with carbohydrate residues.

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Reactions due to side chains

2) Reactions due to SH group (Formation of disulphide bonds)Cysteine has a sulfhydryl group( SH) group and can form a disulphide (S-S) bond with another cysteine residue. The dimer is called CystineTwo cysteine residues can connect two polypeptide chains by the formation of interchain disulphide chains.

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Formation of disulphide bond



3)TransmethylationThe methyl group of Methionine can be transferred after activation to an acceptor for the formation of important biological compounds.

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4)Reactions due to both amino & carboxyl groupsFormation of peptide bond


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Special functions of Amino acids Incorporated in to tissue proteins Niacin, Serotonin and melatonin are synthesized from TryptophanMelanin, thyroid hormone, catecholamines are synthesized from TyrosineGABA (neurotransmitter) is synthesized from Glutamic acidNitric oxide, a smooth muscle relaxant is synthesized from Arginine. Act as precursors for haem, creatine and glutathione, Porphyrins, purines and pyrimidines.

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Colour reactions of amino acidsS.No. Test Significance

1) Ninhydrin reaction Given by all Alpha amino acids

2) Xanthoproteic test Given by aromatic amino acids

3) Millon’s test Confirmatory test for Tyrosine

4) Biuret test Not given by free amino acids

5) Sakaguchi test Given by Arginine

6) Hopkins Cole reaction Confirmatory test for Tryptophan

7) Lead acetate test Given by cysteine and cystine but not given by Methionine

8) Nitroprusside reaction Given by SH group containing amino acids

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chemistry of amino acids

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