Decarboxylase stereochemical mechanism

Scheme X. Stereochemical mechanism for PLP-dependent L-amino acid a-decarboxylases.

Fig. 12. Hypothetical stereochemical mechanism for abortive transamination during the glutamate decarboxylase reaction (261). The same active site base (BH ) is envisioned to be involved in both the normal decarboxylation reaction and abortive transamination.

Fig. 13, Hypothetical stereochemical mechanism for the pyruvyl-containing amino acid decarboxylases consistent with retention of configuration at the a-carbon of the amino acid. The a-carboxyl function is arbitrarily positioned above the si face of the initial ketimine intermediate.

Although an earlier formulation had interpreted the kynureninase reaction in terms of an a,/5-elimination mechanism [142], the available evidence now points to a mechanism paralleling that of aspartate-/5-decarboxylase [141] as proposed by Braunstein [143]. No stereochemical studies have been reported on kynureninase, but some work has been done on aspartate-/5-decarboxylase. 

While the substrate and products of the decarboxylases are achiral (e.g. pyruvate and acetaldehyde or acetate), LThDP and HEThDP are chiral, and knowledge of the stereochemical behavior of these intermediates would provide significant insight to the mechanism. For example, are both enantiomers of LThDP decarboxylated to the enamine, is the enamine converted to only one or both enantiomers of HEThDP and can the enzyme convert only one or both enantiomers of HEThDP to acetaldehyde and ThDP It had been reported that HEThDP isolated from reaction mixtures of PDHc is optically active, suggesting that the enamine is in a chiral environment on the enzyme and protonation is favored from one side . This is a significant finding, yet protonation is only an undesirable side reaction for PDHc. 

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