Purines as 'hyper-repressors' of glucose transport. A role for phosphoribosyl diphosphate

Abstract

Under selected conditions the rate of glucose transport and the intracellular phosphoribosyl diphosphate (PPRibP) concentrations of chick-embryo fibroblasts are inversely correlated. This relationship holds when cells are incubated with mannose, fructose, xylose or various concentrations of glucose. The metabolic inhibitors 2,4-dinitrophenol, rotenone and Methylene Blue increased glucose transport and decreased PPRibP. The addition of any pyrimidine or purine base or ribonucleoside dramatically depleted PPRibP pools, regardless of the carbon source. Addition of guanine (10 microM) or hypoxanthine (100 microM) decreased transport in glucose-grown chick cells to barely detectable values, but did not affect increases observed in cells depressed by substitution of xylose for glucose. Guanosine, inosine and the purine analogues 6-thioguanine, 6-thioguanosine, 8-azaguanine and 6-methylmercaptopurine riboside sharply decreased transport in glucose-grown cells and blocked the increase in transport resulting from the replacement of glucose by fructose or xylose in the culture medium.