Cited by 475Chemical Reaction MechanismsChemical Reactions and MechanismsChemical Reactions and Isotopes

Hydrogen Tunneling in Enzyme Reactions

Cha, Yuan, Murray, Christopher J., Klinman, Judith P.·1989·Science

Abstract

Primary and secondary protium-to-tritium (H/T) and deuterium-to-tritium (D/T) kinetic isotope effects for the catalytic oxidation of benzyl alcohol to benzaldehyde by yeast alcohol dehydrogenase (YADH) at 25 degrees Celsius have been determined. Previous studies showed that this reaction is nearly or fully rate limited by the hydrogen-transfer step. Semiclassical mass considerations that do not include tunneling effects would predict that k H / k T = ( k D / k T )3.26, where k H , k D , and k T are the rate constants for the reaction of protium, deuterium, and tritium derivatives, respectively. Significant deviations from this relation have now been observed for both primary and especially secondary effects, such that experimental H/T ratios are much greater than those calculated from the above expression. These deviations also hold in the temperature range from 0 to 40 degrees Celsius. Such deviations were previously predicted to result from a reaction coordinate containing a significant contribution from hydrogen tunneling.

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Crossref · 10.1126/science.2646716

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  • This enables studying nonadiabatic effects important in DNA mutation and the mechanism of many enzymes.

    “This enables studying the nonadiabatic effects of some systems, which are known to be important in DNA mutation [144] and the mechanism of many enzymes [145].”

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Authors
Cha, Y., Murray, C. J., & Klinman, J. P.
Affiliations
University of California, Berkeley (US)
Venue
Science
Published
1989-03-10
Volume
243
Issue
4896
Pages
1325-1330
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2087123471
Cited by
475
References
30
Citations by year
2026: 12 · 2025: 16 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 9 · 2020: 24 · 2019: 17 · 2018: 10 · 2017: 10 · 2016: 13 · 2015: 17 · 2014: 17 · 2013: 26 · 2012: 18
FWCI
12.74
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Chemical Reactions and Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
Keywords
hydrogen tunneling, kinetic isotope effects, secondary kinetic isotope effects, yeast alcohol dehydrogenase, benzyl alcohol oxidation, benzaldehyde, enzyme catalysis, hydrogen transfer, reaction coordinate, temperature dependence
MeSH terms
Alcohol Dehydrogenase, Benzyl Alcohols, Hydrogen, Kinetics, Mathematics, Models, Theoretical, Oxidation-Reduction, Saccharomyces cerevisiae, Thermodynamics, Tritium

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