期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1978
卷号：75
期号：7
页码：3042-3044
DOI：10.1073/pnas.75.7.3042
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
