Mechanism for enzymatic thioether formation. Mechanism of action of S-adenosylhomocysteinase.

Homogeneous S-adenosylhomocysteinase contains tightly bound NAD+. This NAD+ is not dissociable under nondenaturing conditions but can be removed by heat or acid denaturation. Addition of adenosine to the enzyme causes an increase in the absorption at 327 nm which we attribute to NADH formation. The enzyme also catalyzes the rapid exchange of the adenosine 4'-proton with solvent water. A mechanism is proposed for the reversible hydrolysis of S-adenosyl-L-homocysteine involving oxidation of position 3' of adenosine followed by alpha-beta elimination of L-homocysteine to give 3'-deto-4',5'-dehydro-5'-deoxyadenosine. This compound reacts with water in a Michael-type addition to form 3'-keto adenosine which is then re-reduced to adenosine.