THE MECHANISM OF INACTIVATION OF S-ADENOSYLHOMOCYSTEINE HYDROLASE BY FLUORINATED ANALOGS OF 5'-METHYLTHIOADENOSINE

5'-Deoxy-5'-difluoromethylthioadenosine (DFMTA) la and 5'-deoxy-5'-tri fluoromethylthioadenosine (TFMTA) Ib are inhibitors of beef liver S-ad enosyl-L-homocysteine hydrolase. DFMTA and TFMTA are time-dependent an d irreversible inhibitors of the enzyme. Both la and Ib are oxidized b y E-NAD(+) to produce E-NADH and fluoride anion is formed in the inact ivation reaction (2.2 mol of fluoride/mole of enzyme subunit and 3.1 f luoride/mole of enzyme subunit from DFMTA and TFMTA respectively). Usi ng [8-H-3]-1a or [8-H-3]-1b no trace of labelled adenosine was detecte d during the inactivation reaction but adenine was formed. The mechani sm of inhibition of S-adenosyl-L-homocysteine hydrolase by these two f luorinated nucleosides is discussed.