Mechanistic aspects of biological redox reactions involving NADH. Part 4. Possible mechanisms and corresponding intermediates for the catalytic reaction in L-lactate dehydrogenase

An experimental and computational IR and hybrid DFT-D3 study of the conformations ofl-lactic and acrylic acid: new insight into the dehydration mechanism of lactic acid to acrylic acid

“…12 Formation of the hydrogen bond leads to a stabilisation of 10 +/-4 kcal mol -1 . 13 Spectroscopic evidence of two higher energy conformers come from Fausto and co-workers through matrix isolated Fourier transform-infrared (IR) spectroscopy and theoretical calculations at the DFT(B3LYP)/6-311G(d,p) and MP2/6-31G(d,p) levels of theory which showed that conformer D is the lowest energy structure. 14,15 The same group also studied the structure of lactic acid oligomers (i.e.…”

“…14,15 The same group also studied the structure of lactic acid oligomers (i.e. dimers, trimers and tetramers) using B3LYP/6-311++G(d,p) supported by IR and 1 H/ 13 C NMR studies which found that the most stabilising intermolecular interaction is the O-H A ... O= bond. 16 Banerjee et al…”

Hybrid Quantum and Molecular Mechanical (QM/MM) Studies on the Pyruvate tol-Lactate Interconversion inl-Lactate Dehydrogenase

“…The current hybrid quantum (QM) and molecular (MM) mechanical studies (QM/MM) are the third computational approach we have applied to the LDH mechanism. In initial studies using ab initio QM calculations we found that a proposed reactive intermediate, protonated pyruvate (protonated on carbonyl oxygen), was not a stable species but was in fact a complex of methylhydroxycarbene and carbon dioxide. , This suggested that if such a species was an intermediate in the enzymic reaction, then the carboxyl group must be stabilized by an interaction in the active site, probably with an arginine side chain as indicated by the X-ray structure. In the next stage a “supermolecule” QM approach was used to study the reaction …”

Development of a Potential Surface for Simulation of Proton and Hydride Transfer Reactions in Solution: Application to NADH Hydride Transfer

“…As indicated in Figure , the NADH hydride transfer reaction involves the deprotonation of the alcohol. The order in which the hydride transfer and deprotonation reactions occur is a complex issue. ,, The structural and energetic effects of deprotonation have been studied previously with semiempirical molecular orbital methods to determine transition state structures in the gas phase for both the protonated and deprotonated substrate. , However, solvent effects are expected to significantly alter the energetics of these reactions. We have therefore accumulated results for both protonated and deprotonated forms of the complex.…”

“…A variety of theoretical methods have already been applied to NADH hydride transfer systems. Semiempirical and ab initio calculations have been used to determine the structures, charge distributions, and relative energies of reactants, products, and transition states for model NADH hydride transfer reactions in the gas phase. − These calculations have been useful in determining structural characteristics such as the degree of puckering of the 1,4-dihydronicotinamide ring and the orientation of the 3-amide group in 1,4-dihydronicotinamide. However, such gas phase calculations neglect the effects of the solvent or protein environment, which have been shown to play an important role in proton and hydride transfer reactions…”