Lactylthiamine pyrophosphate

The crystal structures of thiamin-dependent enzymes (see next section) as well as modeling102 103 suggest that lactylthiamin pyrophosphate has the conformation shown in Eq. 14-21. If so, it would be formed by the addition of the ylid to the carbonyl of pyruvate in accord with stereoelectronic principles, and the carboxylate group would also be in the correct orientation for elimination to form the enamine in Eq. 14-21, step b.82 83a A transient 380- to 440-nm absorption band arising during the action of pyruvate decarboxylase has been attributed to the enamine. 

Indeed both -lactylthiamine pyrophosphate (XX) and a-hydroxyethyl-thiamine pyrophosphate (XXI) have been isolated and identified as products after incubation of pyruvate with a purified carboxylase preparation " . When [2- - C]pyruvate is used, the radioactivity is found in the thiazole part of the molecule after sulfite cleavage of XXL Acetaldehyde is formed from pyruvic acid by yeast carboxylase by enzymic cleavage of intermediate XXI, Uberating thiamine pyTophosphate . XXI has also been identified as intermediate in the formation of acetyl-coenzyme A from pyruvic acid by p3u uvic oxidase . The transketolase reaction has been shown to proceed via a gly-colaldehyde-enzyme intermediate here one may expect to find dihydroxy-ethylthiamine pyrophosphate as active glycol-aldehyde . Such experiments strongly support Breslow s concept of the reaction mechanism. 

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