Аннотация:The pyruvate dehydrogenase complex (PDC) connects the two major energetic
mechanisms-glycolysis and the citric acid cycle. The pyruvate dehydrogenase
component (PDH) plays a major role in the functioning and regulation of this
multienzyme complex:
1 . PDH catalyzes the chemical degradation of pyruvic acid with the formation of
carbon dioxide, acetyl residue, and reductive equivalents, which are transferred
in the active centers of dihydrolipoate acetyltransferase (E2) and dihydrolipoate
dehydrogenase (E,) to the terminal acceptors, CoA and NAD.'**
2. PDH carries out the first irreversible and rate-limiting step in the reaction
sequence and thus determines the principal kinetic parameters of the enzyme
complex.
3. Finally, PDH is the main regulatory center of the multienzyme complex.
Activation (dephosphorylation) and inactivation (phosphorylation) of PDC is
carried out by the enzymes phosphatase and kinase, which act on the PDH
component.'
Thus, it was not accidental that Nature has selected the PDH component of the
complex to be a major site of genetic damage to the process of pyruvate oxidative
decarb~xylationS.~tu dy of the properties of PDH is therefore a problem of great
importance for understanding the mechanism for the functioning and regulation of the
PDC. The results of investigations on the active centers of PDH isolated from pigeon
breast muscle PDC are discussed in this report. We have used thiamin analogs,
modification of the side chains of amino acids at the active site, and spectral transitions
to dissect the mechanisms within and interactions between the active centers of the
PDH component.