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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 α-keto acids.
Ammonia is transformed mainly into urea
The α-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 α-amino acid to α-keto acid with
formation of a new α-amino acid and a new α-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.
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α-amino acid
α-keto acid
Transaminase
a new α-keto acid
a new α-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 α-keto acid
α-amino acid
Pyridoxal phosphate
CHO
NH2
HO
R CH COOH
H3C
a new α-amino acid
NH2
CH2 O P
R1 CH COOH
N
Transaminases
CH2-NH2
O
O
R C COOH
α-keto acid
CH2 O P
HO
H3C
R1
C COOH
N
Pyridoxamine phosphate
a new α-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 α-ketoglutaric acid.
• It also catalyzes the reverse reaction.
• It needs pyridoxal phosphate as a coenzyme.
• It is present in the cytoplasm of liver cells.
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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
O
C
CH3
C COOH
CH2 O P
HO
H3C
O
CH2
N
CH2
COOH
Pyruvic acid
Pyridoxamine phosphate
α-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 α-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
N
CH2-NH2
COOH
O
CH2
CH2 O P
HO
H3C
N
COOH
C
O
CH2
CH2
COOH
COOH
Oxalacetic acid
CH2
COOH
AST (GOT)
COOH
C
NH2
Pyridoxamine phosphate
α-ketoglutaric acid
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C. Glutamate transaminase
• It catalyzes the transfer of amino group from any amino acid (except lysine,
threonine, proline and hydroxy proline) to α-ketoglutaric acid to form glutamic
acid and the corresponding α-keto acid
• It also catalyzes the reverse reaction
• It needs pyridoxal phosphate as a coenzyme
• It is widely distributed in all tissues
α-Amino acid
Glutamic acid
Pyridoxal phosphate
HC
CHO
NH2
R CH COOH
COOH
NH2
CH2
CH2 O P
HO
H3C
N
CH2
COOH
Glutamate transaminase
COOH
CH2-NH2
O
R C COOH
α-Keto acid
CH2 O P
HO
H3C
N
Pyridoxamine phosphate
C
O
CH2
CH2
COOH
α-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 α-amino acid in the form of
ammonia with formation of α-keto acid
The liver and kidney are the main sites for deamination
Deamination may be oxidative or non-oxidative
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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
R
C
COOH
R
C COOH
NH
NH2
FMN
L-amino acid
FMNH2
H2O
α-imino acid
NH3
α-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
α-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
α-imino acid
R
C COOH
NH3
α-keto acid
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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 α-ketoglutaric acid and ammonia
COOH
NH2
HC
CH2
Glutamate dehydrogenase
COOH
COOH
C
C
NH
CH2
CH2
NAD
COOH
NADH+H+
Glutamate dehydrogenase
CH2
H2O
COOH
α-iminoglutaric acid
Glutamic acid
O
CH2
CH2
NH3
COOH
α-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
O
Serine dehydratase
C COOH
CH3
C COOH
PLP
H2O
Serine
α-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
α-imino acid
NH3
Pyruvic acid
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Most of the naturally occurring α–amino acids are catabolized by transamination with α–
ketoglutaric acid followed by deamination of the produced glutamic acid, a condition
called transdeamination
α-Amino acid
α-ketoglutaric acid
COOH
C
NH2
Ammonia
O
NH3
CH2
R CH COOH
CH2
COOH
Transaminases
O
HC
R C COOH
Glutamate
dehydrogenase
COOH
NH2
CH2
CH2
COOH
α-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
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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
+
C
O
HO
C
H
H
C
OH
H
C
OH
CH2
CO
NH2
Glutamine
COOH
HC
NH2
CH2
+
CH2
HC
Glutamic acid
C
H
H
C
OH
H
C
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
α-amino acid
Decarboxylase
R CH2 NH2
PLP
CO2
NH2
HO
COOH
CH2 OH
Fructose
CH2OH
Amine