AA metablism

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Urea Biosynthesis
• Transamination.
2. Oxidative Deamination.


3.Ammonia Transport.

4.Urea Cycle

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it is the transfer of amine group (-NH2) from α amino acid to α keto acid catalyzed by a group of enzymes called transaminases enzymes require pyridoxal phosphate (B6) as a coenzymes .
The transfer of amine group from one carbon skeleton to another is catalysed by a group of enzymes called (Aminotransferases) (Transaminases).


These enzymes are found in the cytosol and mitochondria. Of all cells specially liver, kidney, intestine and muscles.
All AA except lysine and threonine enter in the process of transamination at some point of its catabolism.
1.Transamination:

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Only two transaminases are important:
1 Alanin transaminase(ALT).
2 Aspartate transaminase (AST).

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Only two transaminases are important:
1 Alanin transaminase(ALT).
2 Aspartate transaminase (AST).

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1) Alanin Aminotransferases (ALT)
It is also called (Glutamate transaminase (GPT)).
It is present in many tissues but it is mainly concentrated in the liver.
It catalyze the transfer of the amino group of alanin to αketoglutarate ,resulting in the formation of pyruvate and glutamate


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Alanin transaminase(ALT) cont.
It is a reversible reaction,but during amino acid catabolism ,this enzyme functions in the direction of glutamate synthesis ,thus glutamate ,in effects , acts as a collector of nitrogen from alanine.
It require the coenzyme pyridoxal phosphate(B6).
Aminotransferase act by transfering the amino group of an amino acid to the pyridoxal part of the coenzyme to generate pyridoxamine phosphate.
The pyridoxamine form of the coenzyme then react with an
α –ketoacide to from an amino acid , at the same time
regenerating the original aldehyde form of the coenzyme.


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It is important for the production of non- essential amino acids
depending on the requirement of the cell.
Its is an intracellular enzyme with the low level in the blood .
the presence of elevated blood level of ALT indicates damage to cells
rich in this enzyme .

It is elevated (high level in the blood )as a result of cell damage

and release of intracellular enzyme into the blood seen mainly in
all liver dieses but are particularly high in conditions that cause
extensive cell necrosis , such as severe viral hepatitis , toxic
Injury and prolonged circulatory collapse . ALT is more specific
for liver dieses .
2) Aspartate aminotransferases (AST)

It is called glutamate – oxaloacetate transaminase (GOT)

AST transfers amino groups from glutamate to oxaloacetate
forming aspartate which is used as a source of nitrogen in the
urea cycle.

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Aspartate donates its amino group, becoming the a-keto acid oxaloacetate.

a-Ketoglutarate accepts the amino group, becoming the amino acid glutamate.

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Also require the coenzyme pyridoxine phosphate ( a derivative
of vitamin B6 ) . It is also a reversible reaction the equilibrium
Constant Is near one , allowing the reaction to function in both
amino acid degradation throw removal of α – amino groups
( after consumption of a protein – rich meal )
and biosynthesis through addition of amino groups to the
carbon skeletons of α - keto acids (when the supply of amino
acid from the diet is not adequate to meet synthetic needs of
cells).


It is also an intracellular enzyme with a low level found in
Blood representing the release of cellular contents during
normal cell turn over.
The presence of high level of blood AST indicates damage to
Cells rich in this enzyme mainly the myocardium (Myocardial
Infarction) and muscle disorders.

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The amino acids undergo transamination finally concentrate nitrogen in Glutamate.
Glutamate is the only amino acid undergoes oxidative deamination to liberate free NH3 for urea synthesis
2. Oxidative deamination
Is the liberation of ammonia from amino group of amino acid coupled with oxidation. Occurs mostly in kidney and liver, The purpose of this reaction is to produce NH3 for urea synthesis and α ketoacids for variety of reaction(recycling)
The amino group of most of AA are ultimately funneled to glutamate by means of transamination with α-ketoglutrate. by the action of glutamate dehydrogenase enzyme.`


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Oxidative deamination:
Glutamate dehydrogenase requires NAD+ or NADP+ as coenzyme. This is the only enzyme known that has specificity for both type of coenzyme.


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1)Glutamate rapidly undergoes oxidative deamination catalyzed by glutamate dehydrogenase to liberate ammonia using NAD or NADP as a coenzyme.
Glutamate α ketoglutarate
H2O
NH4
NADP+
NADPH+H
Glutamic Dehaydrogenase


Glutamate
Glutamine
NH4
H2O
ATP
ADP +Pi
Glutamine synthetase
2)Glutamine
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Glutamine
Glutamate
Glutaminase
H2O
NH4

Urine

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3)Urea Formation


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After ingestion of protein rich meal . Liver glutamate level is
elevated and the reaction proceeds in the direction of amino acid degradation and the formation of ammonia It is converted to α ketoglutarate with liberation of NH3.

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Further when cellular energy levels are low . The degradation of
glutamate is increased to provide α ketoglutarate which enter
the TCA cycle to produce energy. i.e. the reaction is used to
synthesize amino acids from the corresponding α keto acids
Fig 19-12 B)

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Some amino acids can be deaminated to liberate NH4 without oxidation. Serine, homoserine and threonine ,
they undergo deamination catalysed by the enzyme dehydratase with pyridoxal phosphate as a coenzyme.

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Non oxidative deamination:


dehydratase

NH3
Serine
Threonine respective α ketoacids
Homoserine

Desulfhydrase another enzyme catalysed non oxidative

deamination for sulfur amino acid cysteine and homocysteine

desulfhydrase

NH3+H2S
Histidine Urocanate

Histidinase

NH3

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Cysteine Pyruvate

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3.Ammonia Transport (Metabolic Fate Of
Ammonia): (transport to the liver)
Two mechanism are available for the transport of ammonia
from the peripheral tissues to the liver for its ultimate
conversion to urea .
First uses glutamine synthetase to combine ammonia with
glutamate to form glutamine figure 19 - 13 .


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The glutamine is transported in the blood to the liver where it is
cleaved by glutaminase to produce glutamate and free
ammonia .
second transport mechanism used by muscle involves
transamination of pyruvate to form alanine. Alanine is transported by the blood to the Liver , where it is converted to pyruvate again by transamination .
In the liver the pathway of gluconeogenesis can use the
pyruvate to Synthesize glucose , which can enter the blood
and be used by muscle, a pathway called the glucose –
alanine cycle .

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• Metabolism of Ammonia


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It is not a waste product of nitrogen metabolism . It is involved directly or via glutamine for the synthesis of many compound in the body , these include non-essential amino acids, purines, pyrimidines aspargine. Ammonium ions are very important to maintain acid- base balance in the body.
Function of Ammonia:
Toxicity of ammonia:
Elevation of blood ammonia is toxic to the brain leads to slurred
speech, blurring of vision , tremors it may lead to coma and
finally death.
Hyperammonemia may be:
A. genetic defect in urea synthesis
due to a defective enzyme synthesis in any one of the five
enzymes.


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or B. acquired.
The acquired may be due to hepatitis or alcoholism where urea
synthesis become defective and NH3 accumulates.
Explanation for ammonia toxicity:
The reaction catalyzed by glutamate dehydrogenase may
explain the toxic effect of ammonia in brain .


Glutamate dehydrogenase
α- ketoglutarate + NH3 Glutamate
Accumulation of NH3 shifts the equilibrium to the right with more
glutamate formation. hence more utilization of ketoglutarate and
it is the a key intermediate in TCA cycle .

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The net result is that production of energy (ATP) by the brain is
reduced. The toxic effect of NH3 on brain are therefore due to
impairment in ATP production.


Dietary protein Body protein

Amino Acids

Protein synthesis

transamination

αketoglutarate
Glutamate

NH3

Urea

Deamination

ketoacids

Energy
Glucose
Fat
Non essential amino acids
An overview of amino acid metabolism
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