Inactivation of S-adenosylhomocysteine hydrolase by nucleosides.

The irreversible inactivation of S-adenosylhomocysteine hydrolase purified from hamster and bovine liver by adenosine analogs substituted in the 5' and 2 positions has been investigated in detail. 5'-Cyano-5'-deoxyadenosine inactivates as potently as 9-beta-D-arabinofuranosyladenine (Ara-A). Substitution of the Ara-A at the 2 position by halogens or deleting N at the 3 position decreases its potency. Although weak, 2',3'-dideoxyadenosine can also inactivate the enzyme. The irreversible inactivation of the hydrolase in rat hepatocytes incubated with 2-chloroadenosine or 3-deaza-Ara-A could be demonstrated, concomitant with increases in 35S-labeled S-adenosylhomocysteine and S-adenosylmethionine in the hepatocytes.