- Source: 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.
References
External links
Adenosylhomocysteinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Further reading
Vizán, Pedro; Di Croce, Luciano; Aranda, Sergi (31 March 2021). "Functional and Pathological Roles of AHCY". Frontiers in Cell and Developmental Biology. 9. doi:10.3389/fcell.2021.654344. eISSN 2296-634X. PMC 8044520. PMID 33869213.
Vugrek, Oliver; Belužić, Robert; Nakić, Nikolina; Mudd, S. Harvey (28 January 2009). "S-adenosylhomocysteine hydrolase (AHCY) deficiency: Two novel mutations with lethal outcome". Human Mutation. 30 (4): E555–E565. doi:10.1002/humu.20985. ISSN 1059-7794. PMC 2876820. PMID 19177456.
Chicco, Davide; Sanavia, Tiziana; Jurman, Giuseppe (4 March 2023). "Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma". BioData Mining. 16 (1): 7. doi:10.1186/s13040-023-00325-1. eISSN 1756-0381. PMC 9985261. PMID 36870971.