The metabolism of proline and pyrroline-5-carboxylate (P5C) provides a mechanism for the intercompartmental, intercellular, and interorgan transfer of redox potential. Mediated by the transfer of redox potential, P5C stimulates the pentose phosphate pathway, phosphoribosyl pyrophosphate (PRPP) synthesis, and nucleotide production. This mechanism links amino acid and nucleotide metabolism. This effect of P5C has been shown to be synergistic to the effect of growth factors on ribonucleotide synthesis, and suggests that P5C may mediate hormonal effects and, indeed, may act as a """"""""primitive hormone."""""""" Such a role for P5C as an intercellular communicator has been supported by studies in normal human volunteers. P5C is found in human venous plasma (0.40 +- O.12 MuM). More importantly, the levels are responsive to nutritional perturbation increasing 10-fold to 3-5 MuM following a protein meal. Thus, P5C may serve as a mechanism to link nutritional factors to growth factor action. Finally, P5C has been used as a probe to uncover redox abnormalities in tumor cells resistant to adriamycin. The transfer of oxidizing potential into the pentose phosphate pathway mediated by P5C is 4- to 5-fold greater in adriamycin-resistant cells than in wild type cells.
