Decreased phosphoribosylpyrophosphate as the basis for decreased purine synthesis during amino acid starvation of human lymphoblasts.

Abstract

Rates of de novo and salvage purine synthesis decrease by approximately 80 and 60%, respectively, when normal human lymphoblasts are starved 3 h for an essential amino acid (Boss, G. R., and Erbe, R. W. (1982) J. Biol. Chem. 257, 4242-4247). Amino acid starvation decreased the intracellular phosphoribosylpyrophosphate (PP-Rib-P) and ribose 5-phosphate concentrations by approximately 40%, but neither the specific activities of PP-Rib-P synthetase and glutamine amidophosphoribosyltransferase nor the intracellular concentrations of purine nucleotides and inorganic phosphate changed significantly. In mutant cells with either an increased capacity to generate PP-Rib-P (superactive PP-Rib-P synthetase), or an increased PP-Rib-P concentration (inosinate-guanylate:pyrophosphate phosphoribosyltransferase deficiency), the intracellular PP-Rib-P concentration decreased by less than 15% during amino acid starvation and de novo purine synthesis decreased significantly less than in normal cells. When normal cells were treated with drugs that simultaneously decreased feed-back inhibition by purine nucleotides and increased the intracellular concentration of ribose 5-phosphate and PP-Rib-P rates of de novo purine synthesis were stimulated 3-fold in nonstarved cells and more than 8-fold in starved cells. This greater stimulation in the starved cells appeared to be from the increased PP-Rib-P production; moreover, in starved cells in which the increase of the PP-Rib-P concentration by the drugs was impaired because of purine nucleoside phosphorylase deficiency, rates of de novo purine synthesis increased only 3.5-fold. The data suggest that amino acid starvation decreases purine synthesis by decreasing the generation of PP-Rib-P from glucose.

• Authors: G R Boss
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 259 Issue 5 Pg. 2936-41 (Mar 10 1984) ISSN: 0021-9258 [Print] United States
• PMID: 6199353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amino Acids
• Pentosephosphates
• Purines
• Ribosemonophosphates
• ribose-5-phosphate
• Phosphoribosyl Pyrophosphate
• Pentosyltransferases
• Amidophosphoribosyltransferase
• Phosphotransferases
• Ribose-Phosphate Pyrophosphokinase

Topics

• Amidophosphoribosyltransferase (metabolism)
• Amino Acids (metabolism)
• Cell Line
• Humans
• Kinetics
• Lymphocytes (metabolism)
• Pentosephosphates (metabolism)
• Pentosyltransferases (metabolism)
• Phosphoribosyl Pyrophosphate (metabolism)
• Phosphotransferases (metabolism)
• Purines (biosynthesis)
• Ribose-Phosphate Pyrophosphokinase (metabolism)
• Ribosemonophosphates (metabolism)