Interplay of organic and biological chemistry in understanding coenzyme mechanisms: example of thiamin diphosphate-dependent decarboxylations of 2-oxo acids

With the publication of the three-dimensional structures of several thiamin diphosphate-dependent enzymes, the chemical mechanism of their non-oxidati ve and oxidative decarboxylation reactions is better understood. Chemical m odels for these reactions serve a useful purpose to help evaluate the addit ional catalytic rate acceleration provided by the protein component. The ab ility to generate, and spectroscopically observe, the two key zwitterionic intermediates invoked, in such reactions allowed progress to be made in elu cidating the rates and mechanisms of the elementary steps leading to and fr om these intermediates, The need remains to develop chemical models, which accurately reflect the enzyme-bound conformation of this coenzyme, (C) 1999 Federation of European Biochemical Societies.