Stimulation of the hexosemonophosphate-pentose pathway by pyrroline-5-carboxylate in cultured cells.
delta 1-Pyrroline-5-carboxylic acid, an intermediate in the interconversions of proline, ornithine, and glutamate, is a potent stimulator of glucose oxidation through the hexosemonophosphate-pentose pathway. The effect is observed in cultured human fibroblasts, Chinese hamster ovary cells (CHO-K1), and rabbit kidney cells (LLC-RK1). In human fibroblasts, the magnitude of the stimulation of the hexosemonophosphate-pentose pathway is dependent on the concentration of added pyrroline-5-carboxylate and the effect is observed over a wide range of glucose concentrations. The mechanism of the effect is related to the generation of oxidizing potential in the form of NADP+ by pyrroline-5-carboxylate reductase concomitant with the conversion of pyrroline-5-carboxylate to proline. In LLC-RK1 cells, a cell line unique in having proline oxidase activity, proline also stimulated hexosemonophosphate-pentose pathway activity. Although pyrroline-5-carboxylate markedly stimulated the hexosemonophosphate-pentose pathway, it has no effect on glucose metabolism in the Embden-Meyerhof pathway or the tricarboxylic acid cycle. Since the hexosemonophosphate-pentose pathway is a source of ribose-5-phosphate, the precursor of phosphoribosyl pyrophosphate, the effect of pyrroline-5-carboxylate on the hexosemonophosphate-pentose pathway may link amino acid and nucleic acid metabolism.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002952:Citric Acid Cycle / Q000187:drug effects; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts; D005947:Glucose / Q000378:metabolism*; D006600:Hexosephosphates / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D009249:NADP / Q000378:metabolism; D010053:Ovary; D010084:Oxidation-Reduction; D010429:Pentoses / Q000378:metabolism*; D011392:Proline / Q000494:pharmacology; D011758:Pyrroles / Q000378:metabolism / Q000494:pharmacology*; D011762:Pyrroline Carboxylate Reductases / Q000378:metabolism; D011817:Rabbits
D006600:Hexosephosphates; D010429:Pentoses; D011758:Pyrroles; C015485:delta-1-pyrroline-5-carboxylate; D009249:NADP; D011392:Proline; D011762:Pyrroline Carboxylate Reductases; D005947:Glucose