Differential effects of the NADPH/NADP+ ratio on the activities of hexose-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase.
The steady-state kinetics of rat liver hexose-6-phosphate dehydrogenase (beta-D-glucose: NAD(P)+ 1-oxidoreductase, EC 1.1.1.47) using glucose 6-phosphate and NADP+ as substrates is studied. NADPH has been found to inhibit the enzyme noncompetitively with respect to NADP+, and uncompetitively with respect to glucose 6-phosphate. At a given concentration of glucose 6-phosphate, the reaction follows the basic inhibition equation. This suggests the presence of the enzyme-NADP+-NADPH complex, and contrasts with the NADPH inhibition of glucose-6-phosphate dehydrogenase which is competitive with respect to NADP+. An attempt was made to estimate the in vivo activities of the two enzymes in rat liver in the presence of NADPH at various NADPH/NADP+ ratios. The results show that the two enzymes appear to be at about the same level of activity in normal rat liver where the coenzyme redox ratio is 110 and the glucose 6-phosphate concentration is 217 microM. Under the same conditions, but with 50 microM dehydroepiandrosterone, a potent inhibitor of glucose-6-phosphate dehydrogenase, but not of hexose-6-phosphate dehydrogenase, the latter enzyme is estimated to be 1.6-times as active as the former. Such differential effects of NADPH and steroids on the two enzymes may support our notion that hexose-6-phosphate dehydrogenase may have advantages over glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) in steroid-metabolizing tissues (the activity of hexose-6-phosphate dehydrogenase is not, or less, affected by steroids of NADPH).
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D002413:Cations, Divalent; D004040:Dietary Carbohydrates / Q000494:pharmacology; D005215:Fasting; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011374:Progesterone / Q000494:pharmacology; D051381:Rats
D000728:Androgens; D002413:Cations, Divalent; D004040:Dietary Carbohydrates; D011374:Progesterone; D009249:NADP; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D005954:Glucosephosphate Dehydrogenase