Abstract
This study was aimed at elucidation of the metabolic basis for the marked depletion of GTP in RBC of patients with the hereditary deficiency of HGPRT and PNP. RBC were preincubated with labelled Gu, Ad, or Hx, the cells washed and the dietribution of labelling followed in nucleotides, nucleosides and bases over 3 h. 36% of the counts in Gu nucleotides (GuRN) were lost to IMP, Ino and Hx. The results of inhibition of IMP dehydrogenase by mycophenolic acid suggested that only a negligible proportion of these counts return normally to GMP. 15% of the counts in AdRN were lost through IMP to Ino and Hx, but were not detected in Gu derivatives All the counts originating from Hx remained in Hx derivatives. There was a marked degradation of newly formed IMP to Ino and Hx. The results suggest that in RBC, there is a substantial reduction of GMP to IMP, but that the fluxes from IMP or AMP towards GMP are negligible. Thus, RBC depend mainly on Gu salvage for the maintenance of GuRN pools. Accordingly, GuRN depletion is expected in RBC with deficiencies of the salvage enzymes. (Supported by the USA-Israel BSF).
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