The metabolism of proline and pyrroline-5-carboxylate (P5C) provides a mechanism for the intercompartmental, intercellular, and interorgan transfer of biologic information. The information is in the form of redox potential. (1) The transfer of redox potential by P5C provides a metabolic interlock between amino acids and ribonucleotides, an interlock which is modulated by growth factors as an early event during mitogenesis. The synergistic stimulation of PP-Rib-P synthesis by P5C and platelet-derived growth factor (PDGF) has been characterized in normal human fibroblasts. (2) P5C serves as an intercellular communicator by transferring biologic information from one organ to another. Plasma levels of P5C in humans are responsive to dietary intake and increase 10- to 15-fold with a normal diet as compared to the fasting state. Thus, P5C acts as a nutritionally sensitive """"""""hormone"""""""" to transfer redox potential. (3) P5C reductase, the enzyme which catalyzes this transfer of redox potential, has been purified to homogeneity from human cells for the first time. On the basis of kinetics and regulatory mechanisms, it can be concluded that the enzyme functions primarily to catalyze the P5C-dependent oxidation of NADPH, thereby providing the mechanism for the metabolic interlock.
