The effect of ribose 5-phosphate and 5-phosphoribosyl-1-pyrophosphate availability on de novo synthesis of purine nucleotides in rat liver slices.
The effect of increasing cellular ribose 5-phosphate (ribose-5-P) availability by methylene blue-induced acceleration of the oxidative pentose phosphate pathway on the rate of 5-phosphoribosyl-1-pyrophosphate (P-ribose-PP) generation, was studied in slices of rat liver at varying Pi concentration. It was found that at Pi concentration prevailing in the tissue of extracellular physiological Pi concentration, ribose-5-P availability is saturating for P-ribose-PP generation, as gauged by the rate of adenine incorporation into tissue nucleotides. The effect of altering P-ribose-PP availability on the rate of de novo purine production gauged by the rate of formate incorporation into purines, was also studied. It was found that the physiological P-ribose-PP concentration in rat liver tissue is limiting for purine synthesis de novo. Depletion of cellular P-ribose-PP, achieved by increase of P-ribose-PP consumption, decelerated purine synthesis, while increase of P-ribose-PP availability, achieved by activation of P-ribose-PP synthetase occurring at elevated Pi concentration, resulted in acceleration of purine synthesis.
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010428:Pentosephosphates / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism / Q000494:pharmacology*; D011685:Purine Nucleotides / Q000096:biosynthesis*; D051381:Rats; D012267:Ribosemonophosphates / Q000494:pharmacology*
D010428:Pentosephosphates; D010710:Phosphates; D011685:Purine Nucleotides; D012267:Ribosemonophosphates; D010754:Phosphoribosyl Pyrophosphate