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Metabolism of amino acidsand Urea cycle

General formula of the a-amino acids

Generalities

NH2-CH-COOH

R

Proteins are the polypeptides formed by sequences of amino acids

The amino acids occupy a central position in the metabolism of nitrogenous compounds

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Main amino acid reactions

• By a transamination reaction (1) the amino group is transferred to a-ketoglutarate to form glutamate in a reversible way.

• Glutamate release ammonia through an oxidation reaction.

• The degradation of the amino acids occurs in the mitochondria.

• Most amino acids have their specific transaminase, and those that do nothave can be transformed into other that has.

• (1) Transaminations are reactions involved in both, anabolism and catabolism.

• TRANSAMINATION

• OXIDATIVE DEAMINATION

• DECARBOXYLATION

Transamination reaction

Enzyme: transaminase (aminotransferase) in cytosol

Reaction : transamination(exchange of amine group)

Coenzyme activateur: Pyridoxal Phosphate (PLP)

Reversible

COO-

CHNH2

R

COO -

COR

COO -

COCH2

CH2

COO -

COO -

CHNH2

CH2

CH2

COO -

aKG Glu

PLP

3

Pyridoxal phosphate (PLP)

N

CCH2OP

CH3

HO

H O

N

CCH2OP

CH3

HOH

NH2

Pyridoxal phosphate(PLP)

Pyridoxamine phosphate(PMP)

H

COO-

CHNH2

R

COO-

COR

PLP PMP

a KGGlu

Mechanisme Ping–pong reaction:

1 - fixation of the substrate 1 to theactive site of the enzyme, thenformation of the product which isdetached from the active site

2 - fixation of the substrate 2 to theactive site of the enzyme

Coenzyme associated with numerous enzymes acting on nitrogen compounds - transaminases

- isomerase

- decarboxylase...

Lateral chain degradation

In general, N elimination occurs by transamination (N is stored in Glutamate), then CO2 is liberated by an oxidative decarboxylation :

- Formed a-ketoacides are Krebs or glycolysis intermediates : pyruvate, a-ketoglutarate, OAA…

COOH

CHNH2

CH3

aKG Glu

COOH

CO

CH3

CH3COSCoA

NAD+ NADH

CO2

(PLP)

(LipSS, TPP, FAD)

Transaminase Déshydrogénase

HSCoA

Example

Glutamate (Glu) can then be directly deaminated by oxidative deamination or used for other transaminations.

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Aminoacids catabolism and anabolism are linked to glycolysis and Krebs intermediates

Elimination of nitrogenous from glutamate

Transformation of glutamate (formed by protein degradation or by AA transamination) in α-ketoglutarate and NH4

+

Oxidation coupled to hydrolysis

Enzyme: Dehydrogenase (Glutamate dehydrogenase)

Oxidative deamination

NH4+

NAD+ NADHH2N CHCH2

CH2

COOH

O CCH2

CH2

COOH

COO- COO-

H2O

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After its production, ammoniac (NH4+) can

(ammoniac fate):

• be stored in glutamine

• be used to form Glu from aKG

• be eliminated by the Urea cycle (main)

Storage of NH4+ as glutamine

Coupled reaction: hydrolysis of ATP and condensation ofNH4

+ on glutamate (double transfer)

H2N CHCH2

CH2

COH

O

H2N CHCH2

CH2

CNH2

O

NH4+

ATP ADP + P

Glutamine synthétase

COOH COOH

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Elimination by urea cycle

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Urea cycle: cellular sublocation

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