Side-Chain Elimination and Replacement Reactions

Cystathionine /3-synthetase contains heme as well as pyridoxal phosphate, but this seems to have a regulatory rather than catalytic role the yeast enzyme does not contain heme (Jhee et al., 2000 Kabil et al., 2001). A common genetic polymorphism in human cystathionine /S-synthetase (a 68-base-pair insertion, occurring in about 12% of the general population) is associated with a lower than normal increase in plasma homocysteine after a methionine load in patients with low vitamin Be status, suggesting that the variant enzyme may have higher affinity for its cofactor than the normal form - the reverse of the position in the vitamin Bg responsive genetic diseases discussed in Section 9.4.3 (Tsaietal., 1999). 

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The ring nitrogen of pyridoxal phosphate exerts a strong electron withdrawing effect on the aldimine, and this leads to weakening of all three bonds about the a-carbon of the substrate. In nonenzymic reactions, all the possible pyridoxal-catalyzed reactions are observed - a-decarboxylation, aminotrans-fer, racemization and side-chain elimination, and replacement reactions. By contrast, enzymes show specificity for the reaction pathway followed which bond is cleaved will depend on the orientation of the Schiff base relative to reactive groups of the catalytic site. As discussed in Section 9.3.1.5, reaction specificity is not complete, and a number of decarboxylases also undergo transamination. 

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