General reactions involved in Amino acid Metabolism

Dr. Dhiraj J Trivedi

Reactions of Amino acid metabolism

1. De amination 2. Desulphuration 3. Trans amination

4. Trans methylation

DEAMINATION

Short note on 5marks

Deamination

• DEFINITION: • Deamination is the process by which N- atom of

amino acid is removed as free NH3.

• Types: It can be of two types • 1] Oxidative deamination.• 2] Non-oxidative deamination.

1] OXIDATIVE DEAMINATION:• Site: Liver and Kidney• Coenzymes: Pyridoxal phosphate• Enzymes: D- amino acid oxidases and L - amino acid

oxidases.

• Even though D- amino acids are normally not present in human body their concentration is higher than L- amino acid oxidases in the body.

• L- amino acid oxidases are Flavoprotein. • They are reoxidized at substrate level, directly by

molecular oxygen forming H2O2.

Step-I: The amino acid is first dehydrogenated by Flavoprotein

of L- amino acid oxidase forming α Imino acid.

Step-II Water molecule is added which, decomposes to form

Ketoacid and N is lost as NH3.

1] OXIDATIVE DEAMINATION:

2] Non oxidative deamination:• There are certain amino acids, which can be non-

oxidatively deaminated by specific enzymes.• a] Amino acid dehydrase:

b] Amino acid desulphurase: • Sulphur containing amino acid like Cysteine and

homo-Cysteine are deaminated by primary desulphuration forming imino acid.

• It is then spontaneously hydrolyzed to α keto acid and NH3 is made free.

3] Deamination of L- Glutamic acid:• L- Glutamic acid is not deaminated by L- amino acid oxidase

but it require L- glutamate dehydrogenase. • Reaction: L- glutamate dehydrogenase Act on L- Glutamic

acid to form α imino glutaric acid. Which on addition of molecule of H2O forms NH3 and α keto glutarate.

• Also called as Transdeamination, Reaction is reversible.

TRANS AMINATION Short note on 5marks

Transamination:• Definition: • Transamination is a reversible reaction • α -NH2 group of amino acid is transferred

to α- keto acid, resulting in the formation of new amino acid and a new keto acid.

Thus at the end of reaction donor amino acid becomes new keto acid & The recipient keto acid becomes new amino acid .

Transamination:• Transamination is a reversible reaction.• It is only for intermolecular transfer of

NH2 group. • In this reaction free ammonia is not

released during reaction.• It requires Pyridoxal phosphate , as

coenzyme.

Salient feature of Transamination:• Site of transamination: Principally in all cells

• major tissues Liver, Heart, Kidney and Brain.

• Enzymes: called transaminases or aminotransferases.

• Co-enzymes: Pyridoxal Phosphate (B6-P)

• Substrates: Amino acids & Keto acids

• End product : Keto acid & non essential amino

acids

Salient feature of Transamination:

• Substrates: Amino acids: • Almost all amino acids undergo transfer of

amino group to small or large extent. • Exceptions -- • Lysine , Threonine , Proline and

hydroxyrpoline • do not take part in transamination reaction.

Salient feature of Transamination:

• Keto acids: There are only three keto acids, Ketoglutarate, Pyruvate and Oxaloacetate which acts as recipient molecules in transamination reactions. All three are component of TCA cycle.

• Reversible reaction: • Hence keto acid can be derived from amino acid,

and amino acids can be obtained from Ketoacid.

Mechanism of enzyme action:• Requires Pyridoxal phosphate as co-enzyme.

• Reaction occur in two stages

• 1] Amino group from amino acid is accepted by

Pyridoxal phosphate to form pyridoxamine and amino

acid is converted to keto acid.

• 2] In second stage, Amino group is accepted by Keto

acid from pyridoxamine and gets converted to amino

acid. The Pyridoxal phosphate is regenerated.

Mechanism of enzyme action:

Alanine Pyruvic acid

α-Keto Glutarate Glutamate

Serum Glutamate Pyruvate Transaminase

Pyridoxal phosphate

Examples of Transamination:

Aspartate Oxalo acetate

α-Keto Glutarate Glutamate

Serum Glutamate Oxaloacetate Transaminase

Pyridoxal phosphate

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α-Keto Glutarate

Glutamate

Pyridoxal phosphate

α-Amino group of Various amino acids

α-Keto Glutarate acts as common acceptor of α-Amino group In transaminase reactions

Clinical Significance:• Two transaminases having clinical significance 1. Serum glutamate Pyruvate transaminase is also

named as alenine transaminase (ALT). • Normal level is 5 to 35 IU/L. • Its activity increases in liver diseases.

2. Serum glutamate oxaloacetate transaminase is also named as aspartate transaminase (AST).

• Its normal value is 5 to 40 IU/L. • The increased activity is seen in heart diseases.

Functions of transamination:1] Inter-conversion of amino acid to keto acid

and keto acid to amino acid. This provides non-essential amino acids in the body.

2] Utilization of alpha keto acids when in excess.

3] Prevents toxicity of ammonia as it is not at all released free during reaction.

TRANS METHYLATIONExplain the reaction of transmethylation 5 marks

Trans methylation• An important biological transfer of methyl

group with in amino acids.

• Process similar to transamination.

• The difference is transfer of methyl group

instead amino group.

Trans methylation • DEFINITION:

The transfer of methyl group (-CH3) from active

Methionine to an acceptor molecule is known as

Transmethylation.

• Methionine has to be activated to S- adenosyl

Methionine (SAM) to donate the methyl group.

Trans methylation• All compounds having –CH3 group cannot act as

methyl group donor.

• Methyl group attached to N atom or S atom

becomes active and can become methyl group

donor.

Enzymes & Coenzymes of trans methylation

• Enzymes: • Enzymes involved are collectively known as

methyltransferases or transmethylases.

• Coenzymes: Tetra hydro folate (THF) is a coenzyme

that actively participates in methyl group transfer.

• Vit B12 is also involved in this reaction (makes folate

free).

Significance of Trans methylation:

1] Transmethylation is an essential process since many

biological compounds become functionally active only

after methylation.

2] Transmethylation synthesizes Biologically important

compounds like Choline, Creatine, Epinephrine, Nor-

epinephrine.

Significance of Trans methylation:3] Amino acid residues of protein on methylation control

protein turn over. In fact methylation protect the

proteins from immediate degradation.

4] In plants and animals Transmethylation help to

synthesis certain hormone. ( Epinephrine, Nor

epinephrine)

Significance of Trans methylation:

5] Decrease of Transmethylation will affect synthesis of

choline and in turn phospholipid. This leads to

decreased formation of lipoproteins and accumulation

of lipid in liver causing fatty liver.

6] Choline synthesis is also required for the synthesis of

Acetyl- choline, a neurotransmitter.

IMPORTANT TRANSMETHYLATION REACTIONS:• S-adenosyl Methionine acts as donor of methyl group. • Transmethylation is a type of one carbon metabolic reaction.

Methyl group acceptors Methylated product

Guanido acetate Creatine

Nor-epinephrine Epinephrine

Epinephrine Metanephrine

Ethamolamine Choline

Phosphatidyl Ethamolamine Lecithin Or Phosphatidyl choline

Serine Choline

Acetyl serotonin Melatonin

Homo Cysteine Methionine

Q: What is transmethylation reaction? Give two examples.

• A: Transmethylation: Transfer of methyl group (-CH3) from active Methionine to an acceptor is known as Transmethylation reaction.

• S- Adenosyl methionine (SAM) is active methyl group donor in many transmethylation reactions. Examples are ,

SAMGuanidinoacetate

Creatine

Serine Choline

Nor epinephrine

Epinephrine

S-adenosyl homocysteine

SAM S-adenosyl homocysteine

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