Kinetic and chemical mechanisms of the sheep liver 6-phosphogluconate dehydrogenase

Archives of Biochemistry and Biophysics
N E Price, Paul F Cook

Abstract

A complete kinetic characterization of sheep liver 6-phosphogluconate dehydrogenase including product and dead-end inhibition patterns, primary deuterium isotope effects, and the pH dependence of kinetic parameters has been completed in order to determine the kinetic mechanism and obtain information on the chemical mechanism of the enzyme. A rapid equilibrium random kinetic mechanism has been proposed, with product and dead-end inhibition patterns both being symmetric. Ribulose 5-phosphate and 6-sulfogluconate are both competitive with 6-phosphogluconate (6-PG) and noncompetitive with NADP, and NADPH and ATP-ribose are both competitive with NADP and noncompetitive with 6-phosphogluconate. Equal primary deuterium isotope effects of 1.5-2 on DV, DV/KNADP, and DV/K6-PG with 3-deuterio-6-PG confirm a rapid equilibrium random mechanism and show that hydride transfer is at least partially rate limiting in the overall reaction. The maximum velocity is pH dependent, decreasing at low and high pH with slopes of 1 and -1, respectively, and pK values of 6.4 and 8.6. The V/KNADP and V/K6-PG also decrease at low and high pH with slopes of 1 and -1, giving pK values of 6.8 and 8.7 and of 6.9 and 7.8, respectively. The pH rate profiles are co...Continue Reading

Citations

Jun 16, 2007·BMC Structural Biology·Weiwei HeCong-Zhao Zhou
Mar 22, 2016·Nature Chemical Biology·Ling LiuJoshua D Rabinowitz
Oct 8, 2013·Biochimica Et Biophysica Acta·S HanauF Dallocchio
May 9, 2014·Nature·Jing FanJoshua D Rabinowitz
May 15, 2002·Journal of Biomolecular Screening·Kimberly M Mayer, Frances H Arnold
Mar 31, 2006·The Journal of Physical Chemistry. B·Jianyi Wang, Shuhua Li

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