Abstract
(Z)-4,5′-Didehydro-5′-deoxy-5′-fluoroadenosine (I), 5′-deoxy-5′-difluoroadenosine (II), and 4′,5′-didehydro-5′-deoxy-5′-fluoroarabinosyl-adenosine (III) are inhibitors of rat liver S-adenosyl-L-homocysteine hydrolase. Compounds I and II are time-dependent and irreversible inhibitors of the enzyme. Both I and II are oxidized by E. NAD to produce E. NADH, and fluoride anion is formed in the inactivation reaction (0.7 to 1.0 mole fluoride/mole of enzyme subunit, and 1.7 moles fluoride/mole of enzyme subunit from I and II, respectively). The enzyme is stoichiometrically labeled with [8-3 H]-I, but the label is lost upon denaturation of the protein either with or without treatment of the labeled complex with sodium borohy-dride. The compound III, the arabino derivative of I, is a competitive inhibitor of the enzyme. The mechanism of the inhibition of S-adenosyl-L-homocysteine hydrolase by these inhibitors is discussed.