TRANSITION-STATE THEORETICAL INTERPRETATION OF THE CATALYTIC POWER OFPYRUVATE DECARBOXYLASES - THE ROLES OF STATIC AND DYNAMICAL CONSIDERATIONS

The catalytic power of two thiamin diphosphate (ThDP)-dependent enzyme s, yeast pyruvate decarboxylase (the hysteretically regulated enzyme f rom Saccharomyces cerevisiae, SCPDC) and bacterial pyruvate decarboxyl ase (the unregulated enzyme from Zymomonas mobilis, ZMPDC), are analyz ed by thorough-going application of transition-state theory, i.e. by a static approach that emphasizes the state-function character of the f ree energy of activation and takes no explicit account of dynamical co nsiderations. The overall catalytic reaction is resolved into manifold s for addition (conversion of free enzyme and substrate to the complex of enzyme with the pyruvate:ThDP adduct), decarboxylation, and elimin ation (conversion of the complex of enzyme with the acetaldehyde:ThDP adduct formed by decarboxylation into free product and free enzyme). F or SCPDC, the addition manifold is most strongly catalyzed (3 x 10(12) -fold, corresponding to net transition-state stabilization of 72 kJ/mo l, transition-state stabilization of 83 kJ/mol diminished by reactant- state stabilization of 11 kJ/mol), the decarboxylation manifold is lea st strongly catalyzed (5x10(7)-fold, corresponding to net transition-s tate stabilization of 41 kJ/mol, transition-state stabilization of 68 kJ/mol diminished by reactant-state stabilization of 27 kJ/mol), and t he elimination manifold is catalyzed to an intermediate degree (2 x 10 (10)-fold, corresponding to net transition-state stabilization of 59 k J/mol, transition-state stabilization of 76 kJ/mol diminished by react ant-state stabilization of 17 kJ/mol). A similar situation holds for Z MPDC, There is Ilo need to make an explicit analysis of dynamical fact ors in order to describe the catalytic mechanism and catalytic power o f these complex enzymes. (C) 1998 Elsevier Science B.V. All rights res erved.