Phosphoribosylpyrophosphate synthesis from glucose decreases during amino acid starvation of human lymphoblasts.
When cultured human lymphoblasts are starved 3 h for an essential amino acid, rates of purine nucleotide synthesis decrease markedly because of a decrease in the intracellular phosphoribosylpyrophosphate concentration (Boss, G.R., and Erbe, R.W. (1982) J. Biol. Chem. 257, 4242-4247; Boss, G. R. (1984) J. Biol. Chem. 259, 2936-2941). In amino acid-starved cells, glucose transport was not changed, whereas total glucose consumption and lactate production decreased by approximately 25 and 10%, respectively. Carbon flow through the oxidative pentose phosphate pathway, measured by 14CO2 release from [1-14C]glucose, decreased by 18% during amino acid starvation. However, kinetic studies of ribulose-5-phosphate 3-epimerase and phosphoriboisomerase suggested that the ribulose 5-phosphate produced by this pathway is converted mostly to xylulose 5-phosphate instead of to ribose 5-phosphate so that this pathway produces little phosphoribosylpyrophosphate. The activity of the nonoxidative pentose phosphate pathway, measured by high performance liquid chromatography following the incorporation of [1-14C]glucose into phosphoribosylpyrophosphate, ATP, and GTP, decreased by approximately 55% during amino acid starvation. None of the enzymes of either pathway changed in specific activity during amino acid starvation. We conclude that the nonoxidative pentose phosphate pathway is the major source of phosphoribosylpyrophosphate for purine nucleotide synthesis and that this pathway is regulated by a metabolite which changes in concentration during amino acid starvation.
Boss
G R
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Pilz
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D019747:Aldose-Ketose Isomerases; D000596:Amino Acids / Q000378:metabolism*; D001693:Biological Transport, Active; D002238:Carbohydrate Epimerases / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D010428:Pentosephosphates / Q000096:biosynthesis*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis*; D012274:Ribulosephosphates / Q000378:metabolism
D000596:Amino Acids; D010428:Pentosephosphates; D012274:Ribulosephosphates; C031524:ribulose 5-phosphate; D010754:Phosphoribosyl Pyrophosphate; D002238:Carbohydrate Epimerases; C022553:ribulosephosphate 3-epimerase; D019747:Aldose-Ketose Isomerases; C022548:ribosephosphate isomerase; D005947:Glucose