THE MODULATION OF THE OXIDATIVE PHASE OF THE PENTOSE-PHOSPHATE PATHWAY IN MOUSE-LIVER

The glucose-6-phosphate dehydrogenase from mouse liver is fully inhibi ted in vitro by physiological concentrations of NADPH. This suggests t hat the oxidative phase of the pentose phosphate pathway requires some deinhibitory system, In order to investigate regulation of the pentos e phosphate pathway, various parameters (intermediate concentrations, mass-action ratios of reactions, etc.) were measured in liver from con trol mice and from meal-fed mice. Assays were also carried out to dete ct any molecules causing the reverse of glucose-6-phosphate dehydrogen ase inhibition by NADPH. The liver of meal-fed mice show greater gluco se-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase acti vities. They also had greater concentrations of several metabolic inte rmediates and triglycerides than the control animals (P < 0.001). Thes e results prove that the diet increases the how of the pentose phospha te pathway in a lipogenic sense. The glutathione reductase does not ch ange with the diet, suggesting that this enzyme does not participate i n the modulating process. Unlike rat liver, no molecules causing the r everse of glucose-6-phosphate dehydrogenase inhibition by NADPH were d etected, These data suggest that the increase of flow of the pentose p hosphate pathway during lipogenesis is obtained by an increase in enzy me synthesis.