DEUTERIUM SOLVENT ISOTOPE EFFECTS IN REACTIONS CATALYZED BY ISOCITRATE DEHYDROGENASE

The result of substituting deuterium oxide for water on the rates of the overall and partial reactions catalyzed by the pig heart TPN-dependent isocitrate dehydrogenase has been studied. Although the overall oxidative decarboxylation of isocitrate proceeds 4.9 times as fast in H2O as in D2O, the rate of the separately measured oxalosuccinate decarboxylation reaction is only 1.4-1.7 times greater in water. In contrast, the oxalosuccinate reduction reaction proceeds 5.0 times faster in H2O. These results suggest that dehydrogenation is the slow reaction in the oxidative decarboxylation of isocitrate and that a proton transfer is involved in this rate determining step. © 1969.