Adenosylhomocysteinase

Adenosylhomocysteinase (EC 3.13.2.1, S-adenosylhomocysteine synthase, S-adenosylhomocysteine hydrolase, adenosylhomocysteine hydrolase, S-adenosylhomocysteinase, SAHase, AdoHcyase) is an enzyme that catalyzes the nicotinamide adenine dinucleotide (NAD⁺) dependent, reversible hydrolysis of S-adenosylhomocysteine to homocysteine and adenosine.

S-adenosyl-L-homocysteine + H₂O ⇌ L-homocysteine + adenosine

AdoHcyase is a highly conserved protein with about 430 to 470 amino acids. The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be involved in NAD-binding. AdoHcyase binds one NAD⁺ cofactor per subunit. This protein may use the morpheein model of allosteric regulation.

Overall hydrolysis begins with dehydrogenative oxidation of the 3'-OH of the ribose by NAD⁺ (forming NADH). The resulting ketone is α-deprotonated to the enol before elimination of the homocysteine thiolate. Water then adds to the a,b-unsaturated ketone, before reduction of the resultant ketone by NADH.

AdoHcyase is encoded by the AHCY gene in humans, which is believed to have a prognostic role in neuroblastoma. AdoHcyase is significantly associated with adenosine deaminase deficiency, which classically manifests in severe combine immunodeficiency (SCID). Accumulated adenosine derivatives, dATPs, irreversibly bind to and inhibit AdoHcyase, promoting the buildup of S-adenosyl-L-homocysteine (due to equilibrium constant favors S-adenosyl-L-homocystine), a potent inhibitor of methyl transfer reactions.