The role of 5'-methylthioadenosine phosphorylase in 5'-methylthioadenosine-mediated inhibition of lymphocyte transformation.
To determine if increased 5'-methylthioadenosine phosphorylase activity in activated lymphocytes may be responsible for the decreased inhibitory effect noted when 5'-methylthioadenosine is added after stimulation, the activity of this enzyme was monitored during lymphocyte transformation. A direct correlation existed between the transformation process and 5'-methylthioadenosine phosphorylase activity; the longer the stimulation process progressed, the phosphorylase activity; the longer the stimulation process progressed, the greater the enzyme activity. The 7-deaza analog of 5'-methylthioadenosine, 5'-methylthiotubercidin, was utilized to explore further the role that the phosphorylase may play in the reversal process. 5'-Methylthiotubercidin acted as a potent inhibitor, but not a substrate, of the 5'-methylthioadenosine phosphorylase, and was an even more potent inhibitor of lymphocyte transformation than 5'-methylthioadenosine. However, in direct contrast to the 5'-methylthioadenosine effect, inhibition by 5'-methylthiotubercidin could not be completely reversed. These data suggest the 5'-methylthioadenosine phosphorylase plays an important role in reversing 5'-methylthioadenosine-mediated inhibition and that the potent, nonreversible inhibitory effects of 5'-methylthiotubercidin are due to its resistance to 5'-methylthioadenosine phosphorylase degradation.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003839:Deoxyadenosines; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010430:Pentosyltransferases / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D013872:Thionucleosides / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology
D003839:Deoxyadenosines; D010835:Phytohemagglutinins; D013872:Thionucleosides; C021716:5'-methylthiotubercidin; C008500:5'-methylthioadenosine; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D000241:Adenosine; D014372:Tubercidin; D013936:Thymidine