PMID: 6990968May 13, 1980Paper

Transition-state structure in the yeast alcohol dehydrogenase reaction: the magnitude of solvent and alpha-secondary hydrogen isotope effects

Biochemistry
K M WelshJ P Klinman

Abstract

Solvent and alpha-secondary isotope effects have been measured in the yeast alcohol dehydrogenase reaction, under conditions of a rate-limiting transfer of hydrogen between coenzyme and substrate. Determination of catalytic constants (at saturating concentrations of substrate and coenzyme) in H2O and D2O as a function of pH(D) has allowed the separation of solvent effects on pKa from kcat: delta pKa = pKD--pKH = 0.02--0.21, kH2O/kD2O = 1.20 +/- 0.09 in the direction of p-methoxybenzyl alcohol oxidation, and kH2O/kD2O = 0.50 +/- 0.05 and 0.58 +/- 0.06 for p-methoxybenzaldehyde reducation by NADH and [4-2H]NADH. The small effect of D2O on pKa, which contrasts with the common observation that delta pKa congruent to 0.4--0.6, is tentatively assigned to ionization of an active-site ZnOH2. The near absence of an isotope effect on kcat in the direction of alcohol oxidation rules out a mechanism involving concerted catalysis by an active-site base of hydride transfer. In the direction of aldehyde reduction, the observation of inverse isotope effects on kcat is concluded to reflect displacement of zinc-bound water by substrate to form an inner-sphere complex, subsequent to the E.S complex. Equilibrium alpha-secondary isotope effects, me...Continue Reading

References

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Citations

Oct 29, 2013·Archives of Biochemistry and Biophysics·Daniel RostonAmnon Kohen
Sep 12, 2013·Journal of the American Chemical Society·Daniel Roston, Amnon Kohen
Mar 26, 2009·Journal of the American Chemical Society·James P CollmanYing Yang
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daniel Roston, Amnon Kohen
May 16, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel RostonAmnon Kohen
Jan 1, 1982·CRC Critical Reviews in Biochemistry·W W Cleland
Aug 27, 2014·Biochemistry·Savarimuthu Baskar RajBryce V Plapp
Mar 8, 2016·Journal of Chemical Theory and Computation·Matthew J Varga, Steven D Schwartz
Sep 2, 2000·Biophysical Journal·D B Northrop, Y K Cho
Jun 22, 2019·Annual Review of Biochemistry·Judith P Klinman
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Patrick L Fernandez, Andrew S Murkin
Aug 10, 2006·Chemical Reviews·Zachary D Nagel, Judith P Klinman
Sep 1, 1989·Trends in Biochemical Sciences·J P Klinman
Dec 6, 1994·Biochemistry·B N Leichus, J S Blanchard
Mar 10, 1989·Science·Y ChaJ P Klinman

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