Transaminases catalytic mechanism

D-Amino acid transaminases have been less well characterized but proceed by a similar catalytic mechanism and show similar potential as effective biocatalysts. Further strain development has incorporated amino acid racemases, enabling complete utilization of racemic amino donors. Thus, L-aspartic acid can be used as the n-amino acid donor through use of aspartate racemase within the system. 

Over the years, PLP enzymology has been the subject of several reviews, dealing predominantly with the spectroscopy and chemistry, catalytic mechanisms, evolutionary relationships, structure—function rela-tionships, and reactivity with drugs and inhibitors. The more investigated PLP-enzymes have also been specifically reviewed. These include the transaminases, TRPS, and 0-acetylserine sulfhydrylase (OASS)." °... 

Stereochemical and X-ray crystallographic studies on the transaminases (aminotransferases) have given rise to the clearest picture of the spatial relationship between bound substrates and catalytic residues that may apply generally to the PLP-dependent enzymes. Transamination involves the reversible interconversion of L-a-amino acids and a-keto acids by a double-displacement mechanism involving transiently formed pyridoxamine monophosphate (PMP) [Eq. (47)] ... 

Kynureninase (Figure 11.16) is a pyridoxal phosphate-dependent enzyme, and its activity falls markedly in vitamin deficiency, at least partly because it undergoes a slow mechanism-dependent inactivation that leaves catalytically inactive pyridoxamine phosphate at the active site of the enzyme. The enzyme can only be reactivated if there is an adequate supply of pyridoxal phosphate. This means that in vitamin deficiency there is a considerable accumulation of both hydroxykynurenine and kynurenine, sufficient to permit greater metabolic flux than usual through kynurenine transaminase, resulting in increased formation of kynurenic and xanthurenic acids. 

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