| Abstract: | Studies on the catalytic reaction mechanism of L-lactate dehydrogenase have been carried out by using quantum chemical ab initio calculation at HF/6-31G* level. It is found that the interconversion reaction of pyruvate to L-lactate is dominated by the hydride ion HR- transfer, and the transfers of the hydride ion HR and proton HR are a quasi-coupled process, in which the energy barrier of the transition state is about 168.37 kJ/mol. It is shown that the reactant complex is 87.61 kJ/mol lower, in energy, than the product complex. The most striking features in our calculated results are that pyridine ring of the model cofactor is a quasi-boat-like configuration in the transited state, which differs from a planar conformation in some previous semiempirical quantum chemical studies. On the other hand, the similarity in the structure and charge between the HR transfer process and the hydrogen bonding with lower barrier indicates that the HR transfer process occurs by means of an unusual manner. In addition, in the transition state the electrostatic interaction between the substrate and the active site of LDH is quite strong and the polarization of the carbonyl in the substrate is gradually enhanced accompanying the formation of the transition state. These calculated results are well in accord with the previous experimental studies, and indicate that the charge on the hydride ion HR is only 0.13e in the transition state, which is in agreement with the reported semiempirical quantum chemical calculations. |
