GLUCOSE IS ESSENTIAL FOR PROLIFERATION AND THE GLYCOLYTIC ENZYME-INDUCTION THAT PROVOKES A TRANSITION TO GLYCOLYTIC ENERGY-PRODUCTION

A transition from aerobic to anaerobic metabolism occurs as mitogen-ac tivated thymocytes undergo proliferation. Glucose utilization and lact ate formation increases 18- and 38-fold, respectively, during prolifer ation, The absolute amount of (CO2)-C-14 production by pyruvate dehydr ogenase remains constant, while (CO2)-C-14 production by the tricarbox ylic acid cycle is reduced during transition from a resting to a proli ferating state. Addition of 2,4-dinitrophenol, an agent uncoupling oxi dative phosphorylation, and phenacinemethosulfate, an electron accepto r, provide evidence that the reduction of glucose oxidation in prolife rating thymocytes is caused neither by limitation of the tricarboxylic acid cycle itself nor by an insufficient supply of ADP. Our data sugg est that enhanced cytosolic regeneration of NAD(+) by induction of the glycolytic enzymes during proliferation effectively competes with NAD H transport and its subsequent oxidation in the mitochondria. Mitogen- stimulated rat thymocytes cultured in a conventional medium containing glucose induce their glycolytic enzymes 8-10-fold in the S phase of t he cell cycle and divide within a culture period of 72 h. Replacement of glucose by glutamine, glutamine and ribose, or glutamine and uridin e prevents glycolytic enzyme induction and thymocyte proliferation. Th e effect of glucose on glycolytic enzyme induction cannot be mimicked by 3-O-methylglucose or 2-deoxyglucose. In conclusion, glucose is requ ired for proliferation and the glycolytic enzyme induction that mediat es the transition from oxidative to glycolytic energy production durin g the G(1)/S transition of rat thymocytes.