Stimulation of phosphoribosyl pyrophosphate and purine nucleotide production by pyrroline 5-carboxylate in human erythrocytes.
Recent studies have shown that pyrroline 5-carboxylate, the intermediate in the interconversions of proline, ornithine, and glutamate, can regulate the metabolism of erythrocytes. We now report that the formation of 5-phosphoribosyl 1-pyrophosphate (PP-Rib-P) was markedly stimulated by pyrroline 5-carboxylate in intact red cells. The production of PP-Rib-P is an important point of regulation in nucleotide metabolism. We found that pyrroline 5-carboxylate increased glucose metabolism through the oxidative arm of the pentose shunt, ribose 5-phosphate formation, and PP-Rib-P production and subsequently augmented purine nucleotide production through the salvage pathway in erythrocytes. We now report that pyrroline 5-carboxylate markedly stimulated the net synthesis of inosine monophosphate from hypoxanthine in intact human red cells so that the pool of inosine monophosphate became 20-30% of the total pool of purine nucleotides. Inosine monophosphate has been considered to be a "mobile pool" of purines, i.e. a reservoir from which peripheral tissues can be supplied; the effect of pyrroline 5-carboxylate on the inosine monophosphate pool may be a mechanism for regulating the function of erythrocytes in purine delivery.
Yeh
G C
GC
Endocrinology Section, National Cancer Institute, Bethesda, Maryland 20892.
Phang
J M
JM
D000227:Adenine Nucleotides / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007291:Inosine Monophosphate / Q000097:blood; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D010428:Pentosephosphates / Q000096:biosynthesis*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis*; D011685:Purine Nucleotides / Q000096:biosynthesis*; D011758:Pyrroles / Q000494:pharmacology*; D012265:Ribonucleotides / Q000096:biosynthesis
D000227:Adenine Nucleotides; D001786:Blood Glucose; D010428:Pentosephosphates; D011685:Purine Nucleotides; D011758:Pyrroles; D012265:Ribonucleotides; D007291:Inosine Monophosphate; C015485:delta-1-pyrroline-5-carboxylate; D010754:Phosphoribosyl Pyrophosphate