TRANSAMINATION OF AMINO ACIDS

        Transaminases catalyze the transfer of  -NH2 groups from the amino acids, onto alpha-ketoglutarate.  Many different transaminases are known, and they are generally of broad specificity for amino acids (that is, one enzyme can accept as substrates two or more different amino acids).  All have the same cofactor requirement - pyridoxal phosphate (vitamin B6).

(Two amino acids can be directly deaminated: Serine and Threonine. They do not undergo this process of transamination.)



Schiff base linkages

These occur frequently in metabolic reactions. Some examples:

(1) Glycolysis - in the mechanism of aldolase

(2) Phosphogluconate pathway - in the mechanism of transaldolase

(3) Amino acid degradation - with PLP in transamination reactions

A Schiff base linkage is a covalent linkage, involving imine formation between a free amino group and a carbonyl group (from, e.g. an aldehyde or ketone).

 

Mechanism of transamination

PLP plays a central role here in the interconversion of an amino acid and an alpha-keto acid.

(1) Transaminase binds pyridoxal phosphate in a Schiff-base link to a Lysine residue of enzyme (the attachment is to the epsilon-amino group of the Lysine). This forms an "aldimine".

(2) As a new substrate substrate enters the active site, its amino group displaces the -NH2 of active site Lysine. Then a new Schiff-base link is formed to the alpha-amino group of the substrate, as the active site Lysine moves aside.

(3) There is an electronic rearrangement resulting in shifting the double bond to form a "ketimine".

(4) This is followed by hydrolysis to release PMP and an alpha-keto acid.

(5) PMP combines with alpha-ketoglutarate in a reversal of steps 1-4. The net result is transfer of an amino group to alpha-ketoglutarate, and release of glutamate, while regenerating the PLP-enzyme complex.

 

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