COMPARISON OF THE INHIBITION OF TYPE-A AND TYPE-B S-ADENOSYLHOMOCYSTEINE HYDROLASE - EFFECTS OF COFACTOR CONTENT ON INHIBITION BEHAVIOR ANDNUCLEOSIDE BINDING

The enzyme S-adenosylhomocysteine hydrolase (E.C.3.3.1.1) occurs in tw o forms in bovine liver: Type A, which carries four moles of NAD(+) pe r mole of enzyme tetramer, and Type B, which carries two moles of NAD( +) per mole of tetramer.(1) The inhibition of these two forms of the e nzyme with 2',2'-difluoro-2'-deoxyadenosine has been investigated. The studies examined the binding stoichiometry and stability of the enzym e-inhibitor complexes formed from each type of the enzyme, the degree of NAD(+) reduction and NAD(+) release, and the possibility of covalen t bond formation between the enzyme and the inhibitor. Significant dif ferences in the behavior of the two forms of the enzyme were encounter ed which may have important implications for the design of S-adenosylh omocysteine hydrolase inhibitors as therapeutic agents.