Thiamin diphosphate catalytic mechanisms

Benzoylformate decarboxylase (BFD EC 4.1.1.7) belongs to the class of thiamine diphosphate (ThDP)-dependent enzymes. ThDP is the cofactor for a large number of enzymes, including pyruvate decarboxylase (PDC), benzaldehyde lyase (BAL), cyclohexane-1,2-dione hydrolase (CDH), acetohydroxyacid synthase (AHAS), and (lR,6] )-2-succinyl-6-hydroxy-2,4-cyclohexadiene-l-carboxylate synthase (SHCHC), which all catalyze the cleavage and formation of C-C bonds [1]. The underlying catalytic mechanism is summarized elsewhere [2] (see also Chapter 2.2.3). 

As noted earlier, the conversion of benzoylformic acid to benzaldehyde is catalyzed by the thiamin diphosphate (ThDP)-dependent enzyme BFD. The proposed catalytic mechanism proceeds through two covalent... 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

Although thiamine, a thiazolium salt, contains a pyrimine ring, it is the thiazole ring that is responsible for its biological action, thiamine dihosphate being the coenzyme of decarboxylases. The mechanism of the catalytic decarboxylation (e.g. of pyruvic acid to acetaldehyde) was interpreted by Breslow in 1958. The active species is the N-ylide 12 formed from thiamine diphosphate and basic cell components ... 

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