Nuclear quantum effects and kinetic isotope effects in enzyme reactions

Vardi-Kilshtain, Alexandra; Nitoker, Neta; Major, Dan Thomas

doi:10.1016/j.abb.2015.03.001

Cited by 28 publications

(27 citation statements)

References 187 publications

(274 reference statements)

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“…[5] Thetunnel effect and its relevance for chemistry has been covered in many reviews and even textbooks over the last century.The original reference work is probably the textbook by Bell, [6] with other books and reviews following it. [7][8][9][10][11][12] Further review articles deal with special aspects,s uch as atom tunneling in enzymes [13][14][15] or methods to calculate tunneling rates. [16][17][18][19] Of course,q uantum effects such as Jan Meisner obtained his master's degree in chemistry from the University of Stuttgart.…”

Section: Introductionmentioning

confidence: 99%

Atom Tunneling in Chemistry

2016

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Quantum mechanical tunneling of atoms is increasingly found to play an important role in many chemical transformations. Experimentally, atom tunneling can be indirectly detected by temperature-independent rate constants at low temperature or by enhanced kinetic isotope effects. In contrast, the influence of tunneling on the reaction rates can be monitored directly through computational investigations. The tunnel effect, for example, changes reaction paths and branching ratios, enables chemical reactions in an astrochemical environment that would be impossible by thermal transition, and influences biochemical processes.

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Section: Introductionmentioning

confidence: 99%

Atom Tunneling in Chemistry

2016

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“…Comparison of these values with those determined from computation for different mechanisms is frequently sufficient to establish the catalytic mechanism. Indeed, as computational methods have improved, experimentally determined kinetic isotope effects have come to provide necessary constraints on the structures of transition state structures derived from computation [3, 4]. …”

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confidence: 99%

13C kinetic isotope effects on the reaction of a flavin amine oxidase determined from whole molecule isotope effects

Tormos

Suarez

Fitzpatrick

2016

Archives of Biochemistry and Biophysics

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A large number of flavoproteins catalyze the oxidation of amines. Because of the importance of these enzymes in metabolism, their mechanisms have previously been studied using deuterium, nitrogen, and solvent isotope effects. While these results have been valuable for computational studies to distinguish among proposed mechanisms, a measure of the change at the reacting carbon has been lacking. We describe here the measurement of a 13C kinetic isotope effect for a representative amine oxidase, polyamine oxidase. The isotope effect was determined by analysis of the isotopic composition of the unlabeled substrate, N, N'-dibenzyl-1,4-diaminopropane, to obtain a pH-independent value of 1.025. The availability of a 13C isotope effect for flavoproteincatalyzed amine oxidation provides the first measure of the change in bond order at the carbon involved in this carbon-hydrogen bond cleavage and will be of value to understanding the transition state structure for this class of enzymes.

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“…Finally, it is worth mentioning that several methods that can be employed to calculate KIEs for enzymatic reactions have been developed based on Feynman path integral simulations . The quantum classical path (QCP) by Warshel and coworkers can be considered as the first of them.…”

Section: Methods Based On Path Integral Simulationsmentioning

confidence: 99%

Kinetic isotope effects in chemical and biochemical reactions: physical basis and theoretical methods of calculation

González‐Lafont

Lluch

2016

WIREs Comput Mol Sci

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Kinetic isotope effects (KIEs) are a valuable tool for the analysis of chemical and biochemical reaction mechanisms. Theoretical methods of calculation of those KIEs have been developed with the aim to better understand their experimental behavior. In this review, the physical basis as well as several of those computational approaches to calculate primary hydrogen KIEs is presented. Examples of interesting chemical reactions and relevant enzymatic processes are given to demonstrate how theory is used to interpret those complex kinetic magnitudes. In particular, KIE computations within generalized transition state theory formulations are shown here to explain the temperature dependence of chemical and biochemical KIEs caused by multidimensional quantum effects contributions, such as zero point vibrational energy and quantum tunneling. An unexpected large isotope effect on the phosphorescence emission of an organic reaction is analyzed by means of KIE calculations as a function of energy and including also tunneling corrections. More quantum-based methodologies such as the Multiconfiguration Time-Dependent Hartree method and Feynman path integral simulations are discussed within the context of KIE computations. The special kinetic treatment of proton-coupled electron transfer reactions is also analyzed.

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Nuclear quantum effects and kinetic isotope effects in enzyme reactions

Cited by 28 publications

References 187 publications

Atom Tunneling in Chemistry

Atom Tunneling in Chemistry

13C kinetic isotope effects on the reaction of a flavin amine oxidase determined from whole molecule isotope effects

Kinetic isotope effects in chemical and biochemical reactions: physical basis and theoretical methods of calculation

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