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- W2013157260 abstract "Abstract The synthesis and metabolic fate of purine nucleotides were studied, employing labeled precursors, in cultured fibroblasts obtained from normal subjects and from patients with inborn excessive purine production. The patients were affected with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, with virtually complete deficiency of this enzyme and with superactivity of phosphoribosylpyrophosphate synthetase. The rate of total purine synthesis de novo was accelerated 20-fold in the hypoxanthine-guanine phosphoribosyltransferease deficient cells and by 10-fold in the cells with the phosphoribosylpyrophosphate synthetase superactivity. The proportion of the total labeling in purine nucleotides produced de novo, which was excreted into the incubation medium, was markedly increased in the cells with phosphoribosylpyrophosphate synthetase superactivity, but was similar to normal in the hypoxanthine-guanine phosphoribosyltransferase deficient cells. The labeled IMP produced de novo, or from [ 14 C]hypoxanthine, which was not degraded and excreted, was converted in both normal and mutant cells, mainly into adenine nucleotides, but in the cells with phosphoribosylpyrophosphate synthetase superactivity the conversion of labeled IMP to guanine nucleotides was significantly decreased. In all cells, [ 14 C]adenine and [ 14 C]guanine were incorporated mainly into the respective nucleotide pools, whereas the IMP formed from [ 14 C]hypoxanthine was found to be converted to adenine and guanine nucleotides in proportions similar to those after [ 14 C]formate labeling. The incorporation of adenine was increased in all mutant cells studied. The results support the hypotheses concerning the mechanism of purine overproduction in the two mutations and are in accordance with the operation in vivo of the feedback regulation mechanism at the nucleotide interconversions level. The results also suggest that in cultured fibroblasts, GMP is degraded mainly through guanosine, whereas AMP is degraded mainly through IMP." @default.
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- W2013157260 date "1978-12-01" @default.
- W2013157260 modified "2023-09-26" @default.
- W2013157260 title "Synthesis and metabolic fate of purine nucleotides in cultured fibroblasts from normal subjects and from purine overproducing mutants" @default.
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- W2013157260 doi "https://doi.org/10.1016/0005-2787(78)90286-1" @default.
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