Abstract
Glutamine (GLN) is the amino donor in two reactions of de novo purine synthesis and in the formation of guanylic from xanthylic acid (XMP). When confluent cultures of fibroblasts from normal individuals or from patients with the Lesch-Nyhan syndrome (LN) are maintained in GLN-free medium for 24 hours, their rate of de novo synthesis decreases to one-tenth of control cultures. Addition of GLN causes a 5–15-fold stimulation in both types of cells, but at comparable levels of GLN the rate in LN fibroblasts remains 2–5 times higher than normal. In GLN-free medium, LN cells convert 50% more adenine-14C to nucleotides than do normal cells. Of the radioactivity taken up, 1.1% is diverted to guanine nucleotide synthesis in the normals, and 2.8% in LN fibroblasts (sum of radioactivity in guanine nucleotides, XMP, the corresponding nucleosides and bases). In GLN-free medium, XMP, xanthosine, and xanthine contain 67% of this total in the mutants and 43% in the normals. Addition of GLN brings about a decrease in the total incorporation into the componets of the pathway, but a net increase in guanine nucleotide synthesis, as only 4% of the radioactivity is now found in the xanthine compounds in the mutants and 8.8% in the normals. The results show that the availability of GLN can be rate-limiting not only to de novo purine synthesis, but also to guanine nucleotide formation at the XMP aminase reaction. LN cells appear to be more sensitive to GLN deprivation in this reaction, and yet are solely dependent on it for guanine nucleotide synthesis, as they are grossly deficient in hypoxanthine guanine phosphoribosyltransferase activity.
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Raivio, K., Seegmiller, J. Effects of glutamine on purine metabolism in the lesch-Nyhan syndrome. Pediatr Res 5, 396 (1971). https://doi.org/10.1203/00006450-197108000-00103
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DOI: https://doi.org/10.1203/00006450-197108000-00103