PMID: 6108130Oct 17, 1980Paper

Elucidation of aberrant purine metabolism: application to hypoxanthine-guanine phosphoribosylstransferase- and adenosine kinase-deficient mutants, and IMP dehydrogenase- and adenosine deaminase-inhibited human lymphoblasts

Biochimica Et Biophysica Acta
F F SnyderJ E Seegmiller

Abstract

We propose that the ratio of [14C]formate-labelled purine nucleosides and bases (both intra and extracellular) to nucleic acid purines provides, in exponentially growing cultures, a sensitive index for comparative studies of purine metabolism. This ratio was 4-fold greater for an HGPRT- mutant than for the parental HGPRT+ human lymphoblast line. The major components of the labelled nucleoside and base fraction were hypoxanthine and inosine. By blocking adenosine deaminase activity with coformycin we found that approx. 90% of inosine was formed directly from IMP rather than the route IMP leads to AMP leads to adenosine leads to inosine. The ratio of labelled base + nucleosides to nucleic acids was essentially unchagned for an AK- lymphoblast line and 2-fold greater than control for an HGPRT(-)-KAK- line, demonstrating that a deficiency of adenosine kinase alone has little effect on the accumulation of purine nucleosides and bases. Although adenosine was a minor component of the nucleoside and base fraction, the adenosine fraction increased from 3 to 13% with the addition of coformycin to the HGPRT(-)-AK- line. In the parental and HGPRT- lines, adenosine was shown to be primarily phosphorylated rather than deaminated at concentra...Continue Reading

References

Aug 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·L F ThompsonJ E Seegmiller
Jul 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·R C WillisJ E Seegmiller
Mar 28, 1979·Biochimica Et Biophysica Acta·R B GordonB T Emmerson
Sep 1, 1976·The Journal of Clinical Investigation·F F SnyderJ E Seegmiller
Jul 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·J E LeverJ E Seegmiller
Jun 1, 1971·Biochemical Pharmacology·T J Franklin, J M Cook
Sep 1, 1968·Cancer·J A LevyV Defendi
Aug 1, 1969·Experimental Cell Research·T FriedmannJ H Subak-Sharpe

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