Stimulation of the hexosemonophosphate-pentose pathway by pyrroline-5-carboxylate in cultured cells

J Cell Physiol. 1982 Mar;110(3):255-61. doi: 10.1002/jcp.1041100306.


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.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Citric Acid Cycle / drug effects
  • Cricetinae
  • Female
  • Fibroblasts
  • Glucose / metabolism*
  • Hexosephosphates / metabolism*
  • Humans
  • Kidney
  • NADP / metabolism
  • Ovary
  • Oxidation-Reduction
  • Pentoses / metabolism*
  • Proline / pharmacology
  • Pyrroles / metabolism
  • Pyrroles / pharmacology*
  • Pyrroline Carboxylate Reductases / metabolism
  • Rabbits


  • Hexosephosphates
  • Pentoses
  • Pyrroles
  • delta-1-pyrroline-5-carboxylate
  • NADP
  • Proline
  • Pyrroline Carboxylate Reductases
  • Glucose