Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line.
Inhibition of IMP dehydrogenase (EC 1.2.1.14) by ribavirin causes the normal human lymphoblast to excrete increased amounts of newly formed purine into the culture medium. In order for ribavirin to be active as an inhibitor of the dehydrogenase, this synthetic nucleoside must be phosphorylated. The effect of ribavirin on purine excretion has been determined with a normal lymphoblast line, and with lymphoblast lines deficient in hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyl-transferase, EC 2.4.2.8), in adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20), and in both hypoxanthine phosphoribosyltransferase and adenosine kinase. Resistance to the effect of ribavirin on purine excretion was associated only with those cell lines deficient in adenosine kinase activity. These cell lines have normal deoxyadenosine kinase (ATP:deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) activity. Therefore, the nucleoside kinase activity responsible for ribavirin phosphorylation is adenosine kinase.
D000248:Adenosine Kinase / Q000378:metabolism*; D002460:Cell Line; D005561:Formates / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007042:Hypoxanthines / Q000378:metabolism; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007288:Inosine / Q000378:metabolism; D007291:Inosine Monophosphate / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D012254:Ribavirin / Q000378:metabolism* / Q000494:pharmacology; D012263:Ribonucleosides / Q000378:metabolism*
D005561:Formates; D007042:Hypoxanthines; D010710:Phosphates; D012263:Ribonucleosides; D007291:Inosine Monophosphate; D012254:Ribavirin; D007288:Inosine; D007168:IMP Dehydrogenase; D007041:Hypoxanthine Phosphoribosyltransferase; D010770:Phosphotransferases; D000248:Adenosine Kinase