Abstract
Δ^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 had 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.