Purines hypoxanthine active intermediate

Hypoxanthine, on the other hand, which accounts for only a fifth or so of the urinary uric acid is an active intermediate. It is degraded to xanthine and then to uric add by xanthine oxidase. This enzyme is found mainly in liver, kidney, and bowel, while guanase is widely distributed and would quickly deaminate any guanine formed. The product xanthine is a poor substrate for hypoxanthine phosphoribosyltrans-ferase (HPRT). Most of the hypoxanthine formed is reutiliiced by conversion to inosinic acid. Similar conclusions were reached by Ayvazian and Skupp in 1965 when they administered C-labeled purines to patients (A2). Furthermore, these studies and those earlier studies show that the xanthine is converted to hypoxanthine, presumably at the nucleotide level, and on the basis of what we know about microorganisms, we would assume it to be via guanine nucleotides (M2). Since label was found in urinary 7-methylguanine as early as 4 hours after administration of C-labeled purines, and since methylation of RNA occurs at the macromolecular level (B13), interconversion must be rapid and incorporation of some of these products into nucleic acids must also occur quickly. 

I. Reactions of Hypoxanthine. The fact that hypoxanthine is an active intermediate in normal cells directs attention to the three chemical reactions hypoxanthine can undergo in the mammal (Fig. 2). It can be converted to inosine by reaction of the purine with ribose 1-phosphate catalyzed by purine nucleoside phosphorylase. This reaction is probably primarily a phosphorolytic reaction, in vivo, and converts inosine to hypoxanthine and probably does not function to convert hypoxanthine to inosine. There does exist a limited concentration of... 

Routes have been developed for the synthesis of P-L-didehydrodideoxy-nucleosides in the purine series (60, B=Ade, Gua, Hypoxanthine), and the corresponding hydrogenated compounds, starting from either L-xylose or from D-glutamic acid. The L-nucleoside derivative 61 has been prepared by known methods from L-arabinose, and was converted to p-L-d4C (60, B=Cyt), via 62 as an intermediate. Transglycosylation of 61 with 5-fluorouracil was used to make the L-enantiomer of 5-fluoro-d4C (60, B=5-fluoro-Ura). Some of these L-enantiomers have potent anti-HIV and anti-HBV activity. 

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