Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine.
Adenosylhomocysteine hydrolase from human lymphoblasts binds 2'-deoxy[3H]adenosine tightly. Binding is associated with time-dependent, saturable, irreversible inactivation of catalytic activity which occurs with first order kinetics, suggesting "suicide" inactivation. Adenine arabinoside produces similar inactivation but is more potent. These results suggest a basis for a heretofore unrecognized mechanism of action for these and other analogs of adenosine, in which toxicity results from actions of the nucleosides themselves, rather than from nucleotides to which they may be converted.
D002460:Cell Line; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D011485:Protein Binding; D012435:S-Adenosylhomocysteine; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014740:Vidarabine / Q000494:pharmacology*
D003839:Deoxyadenosines; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; D014740:Vidarabine