5'-Deoxyadenosine metabolism in various mammalian cell lines.
5'-Deoxyadenosine (5'-dAdo) was rapidly cleaved to adenine by cell-free, dialyzed extracts of Chinese hamster ovary (CHO), Novikoff rat hepatoma and HeLa cells in a phosphate-dependent reaction, but not by extracts from L929, L1210 and P388 cells. Radioactivity from [5'-3H]5'-dAdo was incorporated into the acid-soluble pool (uptake) by whole CHO, Novikoff and HeLa cells almost as rapidly as from labeled adenosine or adenine (all at 5 microM extracellular concentration). Radioactivity in the acid-soluble pool was mainly associated with a component identified as 5-deoxyribose-1-phosphate. Compared to ribose-1-phosphate, 5-deoxyribose-1-phosphate was metabolically highly stable. A second labeled component, however, was formed slowly and accumulated mainly in the medium. Its formation was greatly stimulated by hypoxanthine and, under conditions where their deamination was not blocked, by adenosine and 2'- and 3'-deoxyadenosine. The second product was 5'-deoxyinosine synthesized from hypoxanthine and 5-deoxyribose-1-phosphate by purine nucleoside phosphorylase. Cleavage of 5'-dAdo by whole cells was dependent on the continuous removal of the product adenine, since uptake was greatly reduced in cells deficient in adenine phosphoribosyl transferase and 50 microM adenine strongly inhibited 5'-dAdo cleavage. The results are consistent with the view that 5'-dAdo is a substrate for 5'-methylthioadenosine phosphorylase and that its use as a non-metabolizable substrate for the nucleoside transport measurements is limited to cells lacking this enzyme.
D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003839:Deoxyadenosines / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D003839:Deoxyadenosines; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D000248:Adenosine Kinase