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
Short note on 5marks

DEAMINATION
 Deamination
• DEFINITION:
• Deamination is the process by which N- atom of
amino acid is removed as free NH 3.

• 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.
 1] OXIDATIVE DEAMINATION:
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.
 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.
Short note on 5marks
TRANS AMINATION
 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:
 Examples of Transamination:
Alanine Pyruvic acid
Serum Glutamate Pyruvate Transaminase
1
Pyridoxal phosphate
α-Keto Glutarate Glutamate

Aspartate Oxalo acetate

Serum Glutamate Oxaloacetate Transaminase
2
Pyridoxal phosphate
α-Keto Glutarate Glutamate
α-Keto Glutarate acts as
common acceptor of α-Amino group
In transaminase reactions α-Keto Glutarate

α-Amino
group of
Pyridoxal phosphate
Various
amino acids

Glutamate
 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.
Explain the reaction of transmethylation 5 marks
TRANS METHYLATION
 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 (-CH 3) 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 ,

1 Guanidinoacetate Creatine
SAM S-adenosyl
2 Serine homocysteine
Choline

3 Nor epinephrine Epinephrine

SAM S-adenosyl
homocysteine