Increase in phosphoribosyl pyrophosphate induced by ATP and P i depletion in hepatocytes

A series of compounds that induce depletion of ATP and P i when added to isolated rat hepatocytes were found to cause a remarkable, although transient, elevation in the concentration of phosphoribosyl pyrophosphate (PRPP) in these cells. After the addition of 5 mM fructose, xylitol, tagatose, or d ‐xylulose, PRPP increased from a basal value of 6 ± 1 nmol/g of cells to, respectively, 68 ± 11, 42 ± 11, 67 ± 22, and 530 ± 50 nmol/g of cells (means ± SEM of 3‐9 experiments). In each case, the increase in PRPP was preceded by a latency period of 5‐10 min. PRPP reached maximal levels 15 min after the addition of fructose and 30 min after that of xylitol and d ‐xylulose, but continued to increase for as long as 60 min after the addition of tagatose. Most striking was that the increase in PRPP closely paralleled the restoration of intracellular P i . Ribose 5‐P increased about two‐ to fivefold after the addition of fructose, xylitol, and tagatose, and approximately 12‐fold after d ‐xylulose. The mechanism by which ATP‐ and Pi‐depleting compounds stimulate the activity of PRPP synthetase in isolated rat hepatocytes is discussed.—V incent , M. E.; V an den B erghe , G.; H ers , H‐G. Increase in phosphoribosyl pyrophosphate induced by ATP and P i depletion in hepatocytes. FASEB J. 3: 1862‐1867; 1989.