Hydrogen Tunneling in Enzyme Reactions
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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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].”
From The prospects of quantum computing in computational molecular biology (2021) · cites this paper as [145]
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- Authors
- Cha, Y., Murray, C. J., & Klinman, J. P.
- Affiliations
- University of California, Berkeley (US)
- ORCID
- Klinman, Judith P.
- 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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