Path Integral Simulation of the H/D Kinetic Isotope Effect in Monoamine Oxidase B Catalyzed Decomposition of Dopamine

2016 ◽  
Vol 120 (14) ◽  
pp. 3488-3492 ◽  
Author(s):  
Janez Mavri ◽  
Ricardo A. Matute ◽  
Zhen T. Chu ◽  
Robert Vianello
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Path Integral ◽  
Kinetic Isotope Effect ◽  
Monoamine Oxidase B ◽  
Kinetic Isotope

scholarly journals Deuterium Kinetic Isotope Effect Studies of a Potential in Vivo Metabolic Trapping Agent for Monoamine Oxidase B

2018 ◽  
Vol 9 (12) ◽  
pp. 3024-3027 ◽  
Author(s):  
Lindsey R. Drake ◽  
Allen F. Brooks ◽  
Anthony J. Mufarreh ◽  
Jonathan M. Pham ◽  
Robert A. Koeppe ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Monoamine Oxidase B ◽  
Kinetic Isotope ◽  
Trapping Agent

scholarly journals Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4359 ◽  
Author(s):  
Mateusz Z. Brela ◽  
Alja Prah ◽  
Marek Boczar ◽  
Jernej Stare ◽  
Janez Mavri
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Path Integral ◽  
Kinetic Isotope Effect ◽  
Monoamine Oxidase A ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Hydrogen Deuterium ◽  
Rate Limiting

Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values.

Kinetic isotope effect in malonaldehyde determined from path integral Monte Carlo simulations

2014 ◽  
Vol 16 (1) ◽  
pp. 204-211 ◽  
Author(s):  
Jing Huang ◽  
Marcin Buchowiecki ◽  
Tibor Nagy ◽  
Jiří Vaníček ◽  
Markus Meuwly
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Isotope Effect ◽  
Path Integral ◽  
Kinetic Isotope Effect ◽  
Path Integral Monte Carlo ◽  
Kinetic Isotope

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

2020 ◽  
Vol 22 (13) ◽  
pp. 6838-6847 ◽  
Author(s):  
Alja Prah ◽  
Peter Ogrin ◽  
Janez Mavri ◽  
Jernej Stare
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Quantum Effects ◽  
Monoamine Oxidase A ◽  
Computational Techniques ◽  
Nuclear Motion ◽  
Enzymatic Reactions ◽  
Kinetic Isotope ◽  
Nuclear Quantum Effects

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.

Quantum electrocatalysts: theoretical picture, electrochemical kinetic isotope effect analysis, and conjecture to understand microscopic mechanisms

2020 ◽  
Vol 22 (20) ◽  
pp. 11219-11243 ◽  
Author(s):  
Ken Sakaushi
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Effect Analysis ◽  
Kinetic Isotope

The fundamental aspects of quantum electrocatalysts are discussed together with the newly developed electrochemical kinetic isotope effect (EC-KIE) approach.

scholarly journals l-mandelate dehydrogenase from Rhodotorula graminis: comparisons with the l-lactate dehydrogenase (flavocytochrome b2) from Saccharomyces cerevisiae

1993 ◽  
Vol 290 (1) ◽  
pp. 103-107 ◽  
Author(s):  
O Smékal ◽  
M Yasin ◽  
C A Fewson ◽  
G A Reid ◽  
S K Chapman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Lactate Dehydrogenase ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Dimensional Structure ◽  
Striking Difference ◽  
Kinetic Properties ◽  
Proton Abstraction ◽  
Rate Determining Step ◽  
Kinetic Isotope

L-Lactate dehydrogenase (L-LDH) from Saccharomyces cerevisiae and L-mandelate dehydrogenase (L-MDH) from Rhodotorula graminis are both flavocytochromes b2. The kinetic properties of these enzymes have been compared using steady-state kinetic methods. The most striking difference between the two enzymes is found by comparing their substrate specificities. L-LDH and L-MDH have mutually exclusive primary substrates, i.e. the substrate for one enzyme is a potent competitive inhibitor for the other. Molecular-modelling studies on the known three-dimensional structure of S. cerevisiae L-LDH suggest that this enzyme is unable to catalyse the oxidation of L-mandelate because productive binding is impeded by steric interference, particularly between the side chain of Leu-230 and the phenyl ring of mandelate. Another major difference between L-LDH and L-MDH lies in the rate-determining step. For S. cerevisiae L-LDH, the major rate-determining step is proton abstraction at C-2 of lactate, as previously shown by the 2H kinetic-isotope effect. However, in R. graminis L-MDH the kinetic-isotope effect seen with DL-[2-2H]mandelate is only 1.1 +/- 0.1, clearly showing that proton abstraction at C-2 of mandelate is not rate-limiting. The fact that the rate-determining step is different indicates that the transition states in each of these enzymes must also be different.

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