Understanding Biological Hydrogen Transfer Through the Lens of Temperature Dependent Kinetic Isotope Effects

Accounts of Chemical Research
Judith P Klinman, Adam R Offenbacher

Abstract

Hydrogen atom transfer (HAT) is a salient feature of many enzymatic C-H cleavage mechanisms. In systems where kinetic isolation of HAT is achieved, selective labeling of substrate with hydrogen isotopes, such as deuterium, enables the determination of intrinsic kinetic isotope effects (KIEs). While the magnitude of the KIE is itself informative, ultimately the size of the temperature dependence of the KIE, Δ Ea = Ea(D) - Ea(H), serves as a critical, and often misinterpreted (or even ignored) descriptor of the reaction coordinate. As will be highlighted in this Account, Δ Ea is one of the most robust parameters to emerge from studies of enzyme catalyzed hydrogen transfer. Kinetic parameters for C-H reactions via HAT can appear consistent with either classical "over-the-barrier" or "Bell-like tunneling correction" models. However, neither of these models is able to explain the observation of near-zero Δ Ea values with many native enzymes that increase upon extrinsic or intrinsic perturbations to function. Instead, a full tunneling model has been developed that can account for the aggregate trends in the temperature dependence of the KIE. This model is reminiscent of Marcus-like theory for electron tunneling, with the additional i...Continue Reading

References

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Dec 9, 2008·Journal of the American Chemical Society·Sudhir C Sharma, Judith P Klinman
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Apr 29, 2010·The Journal of Physical Chemistry. B·Sarah J EdwardsSharon Hammes-Schiffer
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Citations

Mar 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana Karković MarkovićStanko Uršić
Jul 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Adam R Offenbacher, Theodore R Holman
Jun 22, 2019·Annual Review of Biochemistry·Judith P Klinman
Apr 23, 2021·Accounts of Chemical Research·Rahul Banerjee, John D Lipscomb
Aug 20, 2019·Biochemistry·Jiayue LiChristopher M Cheatum
Nov 30, 2019·Journal of the American Chemical Society·Chen-Hao WangDavid C Powers
Jul 18, 2019·The Journal of Physical Chemistry. B·Joel J RiveraJudy E Kim
Dec 6, 2018·The Journal of Physical Chemistry. B·Dmitry V Matyushov, Marshall D Newton
Jun 24, 2020·Journal of the American Chemical Society·Cody R CarrLouise A Berben

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