Nuclear quantum effects in enzymatic reactions: simulation of the kinetic isotope effect of phenylethylamine oxidation catalyzed by monoamine oxidase A

Abstract

By using computational techniques for quantizing nuclear motion one can accurately reproduce kinetic isotope effect of enzymatic reactions, as demonstrated for phenylethylamine oxidation catalyzed by the monoamine oxidase A enzyme.

Questions in the Chemical Enzymology of MAO

“…That the slowest step in the MAO reaction is the reductive half-reaction (oxidation of substrate amine to imine) is clear from studies involving deuterated substrates where large kinetic isotope effects of 5-14 were obtained [25,46,48,[68][69][70][71]. However, the oxidative half-reaction of MAO measured in isolation is slower than the observed steady-state turnover rate for many substrates [45].…”

Simulation of Nuclear Quantum Effects in Condensed Matter Systems via Quantum Baths

“…If t 0 is in a distant past, the first term vanishes. Moreover, if the bath oscillators are assumed to be initially (i.e., at t 0 ) in thermal equilibrium, the random force autocorrelation function can be shown to obey the second-kind FDT of Equations ( 7) and (8).…”

“…These conditions are met, in particular, in systems containing light atoms and most notably hydrogen [4,5], which is a ubiquitous constituent of inorganic compounds and a basic element in biological systems. Thus, nuclear quantum effects influence, for example, the stability of crystal polymorphs of pharmaceutical interest, the spectroscopy of ice and water, or enzymatic reactions in living organisms [6][7][8][9]. NQEs are also required to reveal the effect of isotopic substitutions on equilibrium properties, as a classical description of the nuclei predicts identical statistical properties for all isotopes.…”

Influence of local microenvironment on the double hydrogen transfer in porphycene

“…At the same time reactions involving hydrogen transfer are extremely widespread both in nature and in artificial chemical systems. In the first place they underlie the molecular machinery of life, occurring during numerous enzyme-catalysed reactions [5][6][7] or DNA mutation processes [8][9][10] . On the other hand, hydrogen rearrangement is considered as a promising mechanism underlying operation of molecular switchesbasic components used in the emerging field of nanoelectronics 11 .…”

“…It has been pointed out that better understanding of tunnelling in proton or hydrogen transfer reactions may create a chance for innovations such as an efficient control of the reactions' course 15 , artificial (more efficient) enzymes 16 or fast charging lithium-ion batteries 17 . Therefore, a constant effort is put into development of more accurate models that can be used to describe proton and hydrogen transfer reactions 7,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] . Consequently, the experimental data that can be used to verify new models can be invaluable.…”