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Amino acids pool

The amount of free amino acids distributed throughout the body is called amino acid pool.
Plasma level for most amino acids varies widely throughout the day. It ranges between 4
8 mg/dl.
It tends to increase in the fed state and tends to decrease in the post absorptive state.

Sources of amino acid pool

1.Dietary protein
2.Breakdown of tissue proteins
3.Biosynthesis of nonessential amino acids

Fate of amino acid pool

1.Biosynthesis of structural proteins e.g. tissue proteins
2.Biosynthesis of functional proteins e.g. haemoglobin, myoglobin, protein hormones and
enzymes
3- Biosynthesis of small peptides of biological importance e.g. glutathione, endorphins
and enkephalins
4- Biosynthesis of non protein nitrogenous compounds (NPN) as urea, uric acid, creatine,
creatinine and ammonia
5- Catabolism of amino acids to give ammonia and -keto acids.
Ammonia is transformed mainly into urea
The -keto acids that remain after removal of ammonia from amino acids are called the
carbon skeleton.

Catabolic pathways of amino acids

1.Transamination
2.Deamination
3.Transamidination
4.Transamidation
5.Decarboxylation

1- Transamination
Transamination means transfer of amino group from -amino acid to -keto acid with
formation of a new -amino acid and a new -keto acid.
The liver is the main site for transamination.
All amino acids can be transaminated except lysine, threonine, proline and hydroxy
proline.
All transamination reactions are reversible.
It is catalyzed by aminotransferases (transaminases).
It needs pyridoxal phosphate as a coenzyme.

-amino acid

-keto acid

Transaminase
a new -keto acid

a new -amino acid

Role of pyridoxal phosphate in transamination

Pyridoxal phosphate acts as an intermediate carrier for amino group
Pyridoxal phosphate accepts the amino group from amino acid to form pyridoxamine
phosphate, which in turn gives the amino group to -keto acid

-amino acid

Pyridoxal phosphate
CHO

NH2

HO

R CH COOH

H3C

a new -amino acid

NH2

CH2 O P

R1 CH COOH
N

Transaminases
CH2-NH2

O
R C COOH

-keto acid

CH2 O P

HO
H3C

R1

C COOH

Pyridoxamine phosphate

a new -keto acid

Examples of transaminases
A. Alanine transaminase
B. Aspartate transaminase
C. Glutamate transaminase
A. Alanine transaminase (ALT)
It is also called glutamic pyruvic transaminase (GPT).
It catalyzes the transfer of amino group from glutamic acid to pyruvic acid to form
alanine and -ketoglutaric acid.
It also catalyzes the reverse reaction.
It needs pyridoxal phosphate as a coenzyme.
It is present in the cytoplasm of liver cells.

Alanine

Pyridoxal phosphate

Glutamic acid
COOH

CHO

NH2
CH3 CH

H3C

NH2

CH2

CH2 O P

HO

COOH

HC

CH2
N

COOH

ALT (GPT)

COOH

CH2-NH2

CH3

C COOH

CH2 O P

HO
H3C

CH2

CH2
COOH

Pyruvic acid

Pyridoxamine phosphate

-ketoglutaric acid

B. Aspartate transaminase (AST)

It is also called glutamic oxalacetic transaminase (GOT)
It catalyzes the transfer of amino group from glutamic acid to oxalacetic acid to
form aspartic acid and -ketoglutaric acid
It also catalyzes the reverse reaction
It needs pyridoxal phosphate as a coenzyme
It is present in liver, heart and skeletal muscle cells.
It is present in both cytoplasm and mitochondria

Aspartic acid

Pyridoxal phosphate

Glutamic acid
COOH
HC

CHO

CH2

COOH
HC

NH2

CH2

CH2 O P

HO
H3C

CH2-NH2

COOH
O

CH2

CH2 O P

HO
H3C

COOH
C

CH2
CH2
COOH

COOH

Oxalacetic acid

CH2
COOH

AST (GOT)

COOH

NH2

Pyridoxamine phosphate

-ketoglutaric acid

C. Glutamate transaminase
It catalyzes the transfer of amino group from any amino acid (except lysine,
threonine, proline and hydroxy proline) to -ketoglutaric acid to form glutamic
acid and the corresponding -keto acid
It also catalyzes the reverse reaction
It needs pyridoxal phosphate as a coenzyme
It is widely distributed in all tissues

-Amino acid

Glutamic acid
Pyridoxal phosphate

HC

CHO

NH2
R CH COOH

COOH
NH2

CH2
CH2 O P

HO
H3C

CH2
COOH

Glutamate transaminase
COOH
CH2-NH2

O
R C COOH

-Keto acid

CH2 O P

HO
H3C

Pyridoxamine phosphate

CH2
CH2
COOH

-ketoglutaric acid

Clinical significance of serum transaminases

Transaminases are intracellular enzymes.
Their levels in blood plasma are low under normal conditions.
ALT (GPT) is present mainly in the cytoplasm of liver cells.
AST (GOT) is present in both cytoplasm and mitochondria in liver, heart and skeletal
muscles.
Any damage to these organs will increase the level of transaminases in blood
In liver diseases, there is an increase in both serum ALT (SGPT) and AST (SGOT) levels.
In acute liver diseases, e.g. acute viral hepatitis, the increase is more in SGPT
In chronic liver diseases, e.g. liver cirrhosis the increase is more in SGOT.
In heart diseases, e.g. myocardial infarction, there is an increase in SGOT only.
In skeletal muscle diseases, e.g. myasthenia gravis, there is an increase in SGOT only.

3- Deamination
Deamination means the removal of amino group from -amino acid in the form of
ammonia with formation of -keto acid
The liver and kidney are the main sites for deamination
Deamination may be oxidative or non-oxidative

A. Oxidative deamination
It is catalyzed by one of the following enzymes:
1- L-amino acid oxidases
2- D-amino acid oxidases
3- Glutamate dehydrogenase
B. Non-oxidative deamination
It is catalyzed by one of the following enzymes:
1- Dehydratases
2- Desulfhydrases

A. Oxidative deamination
1- L amino acid oxidase

This enzyme is present in the liver and kidney. Its activity is low.
It is an aerobic dehydrogenase that needs FMN as a coenzyme.
It deaminates most of the naturally occurring L-amino acids

L-amino acid oxidase O

L-amino acid oxidase

R CH COOH

COOH

C COOH

NH

NH2

FMN
L-amino acid

FMNH2

H2O
-imino acid

NH3

-keto acid

2- D amino acid oxidase

NH2

D- amino acids are present in plants and bacterial cell wall.

They are not used in protein biosynthesis in humans and animals.
D-amino acids are deaminated by D-amino acid oxidase resulting in ammonia and
-keto acids.
D-amino acid oxidase is present in the liver.
It is an aerobic dehydrogenase.
It needs FAD as a coenzyme.

D-amino acid oxidase

R CH COOH

FAD
D-amino acid

NH

D-amino acid oxidase O

R CH COOH

H2O
FADH2
-imino acid

C COOH

NH3
-keto acid

3-Glutamate dehydrogenase

This enzyme is present in most tissues

It is present both in cytoplasm and mitochondria
Its activity is high
It is an anaerobic dehydrogenase
It needs NAD or NADP as a coenzyme
It deaminates glutamic acid resulting in -ketoglutaric acid and ammonia

COOH
NH2

HC
CH2

Glutamate dehydrogenase

COOH

COOH

NH

CH2

CH2
NAD

COOH

NADH+H+

Glutamate dehydrogenase

CH2

H2O

COOH
-iminoglutaric acid

Glutamic acid

CH2
CH2

NH3

COOH
-ketoglutaric acid

B.Non-oxidative deamination
1-Dehydratase
This enzyme deaminates amino acids containing hydroxyl group e.g. serine, homoserine
and threonine.
It needs pyridoxal phosphate as coenzyme.

OH NH2
CH2

Serine dehydratase
CH3
CH COOH

NH

Serine dehydratase

C COOH

CH3

C COOH

PLP
H2O

Serine

-imino acid

H2O

NH3
Pyruvic acid

2-Desulfhydrase
This enzyme deaminates sulpher containing amino aids e.g. cysteine and cystine.
It needs pyridoxal phosphate as a coenzyme.

SH NH2

NH

Desulfhydrase

CH2 CH COOH

CH3

Desulfhydrase

C COOH

CH3

O
C COOH

PLP
H2S
Cysteine

H2O
-imino acid

NH3
Pyruvic acid

Most of the naturally occurring amino acids are catabolized by transamination with
ketoglutaric acid followed by deamination of the produced glutamic acid, a condition
called transdeamination

-Amino acid

-ketoglutaric acid
COOH
C

NH2

Ammonia

NH3

CH2

R CH COOH

CH2
COOH

Transaminases
O

HC

R C COOH

Glutamate
dehydrogenase

COOH
NH2

CH2
CH2
COOH

-Keto acid

Glutamic acid

3-Transamidination
Transamidination means the transfer of amidine group from a donor molecule to an
acceptor molecule
It is catalyzed by transamidinase enzyme
An example of transmidination reaction is the transfer of amidine group from arginine
(donor) to glycine (acceptor) in creatine biosynthesis
NH2

HN
C

NH2
NH

CH2

CH2
CH2

+ H2N CH2

CH2
HC

Transamidinase
COOH

CH2
CH2
HC

NH2

Glycine

+
NH2

COOH

COOH

Arginine

NH2

HN

Ornithine

C
HN CH2 COOH

Guanidoacetic acid

4-Transamidation
Transamidation means transfer of amide group nitrogen from a donor molecule to an
acceptor molecule
It is catalyzed by transamidase enzyme
Examples of transmidation reaction include:
1- Transfer of amide nitrogen from glutamine (donor) to fructose (acceptor) to
form glucosamine
2-Amide group nitrogen of glutamine is the source of N3 and N9 in purine bases

Glucosamine biosynthesis
CH2OH

COOH
HC

NH2

CH2

HO

OH

OH

CH2
CO

NH2

Glutamine

COOH
HC

NH2

CH2

CH2

HC

Glutamic acid

OH

OH

CH2 OH

Glucosamine

5-Decarboxylation
Decarboxylation means removal of CO2 from amino acid with formation of
corresponding amines
It is catalyzed by decarboxylase enzyme
It needs pyridoxal phosphate as a coenzyme
Examples of decarboxylation reaction include:
1. Decarboxylation of histidine to form histamine
2. Decarboxylation of tyrosine to form tyramine

NH2
R CH COOH

-amino acid

Decarboxylase

R CH2 NH2

PLP
CO2

NH2

HO

COOH

CH2 OH

Fructose

CH2OH

Amine