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-adenosylhomocysteinetohomocysteine and adenosine.^[2]^[3]

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

AdoHcyase is a highly conserved protein^[4] 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.^[5]

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,^[6]^[7] which is believed to have a prognostic role in neuroblastoma.^[8] 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-homocystine (due to equilibrium constant favors S-adenosyl-L-homocystine), a potent inhibitor of methyl transfer reactions.^[9]

References[edit]

^ Hu Y, Komoto J, Huang Y, et al. (June 1999). "Crystal structure of S-adenosylhomocysteine hydrolase from rat liver". Biochemistry. 38 (26): 8323–33. doi:10.1021/bi990332k. PMID 10387078.

^ De La Haba G, Cantoni GL (March 1959). "The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine". The Journal of Biological Chemistry. 234 (3): 603–8. doi:10.1016/S0021-9258(18)70253-6. PMID 13641268.

^ Palmer JL, Abeles RH (February 1979). "The mechanism of action of S-adenosylhomocysteinase". The Journal of Biological Chemistry. 254 (4): 1217–26. doi:10.1016/S0021-9258(17)34190-X. PMID 762125.

^ Sganga MW, Aksamit RR, Cantoni GL, Bauer CE (1992). "Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteine hydrolase from Rhodobacter capsulatus". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6328–6332. Bibcode:1992PNAS...89.6328S. doi:10.1073/pnas.89.14.6328. PMC 49494. PMID 1631127.

^ T. Selwood; E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.

^ GeneCards.org - AHCY Gene - Adenosylhomocysteinase

^ NLM - AHCY adenosylhomocysteinase

^ 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.

^ Hershfield, M S (1979). "In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients". J Clin Invest. 63 (4): 807–811. doi:10.1172/JCI109367. PMC 372019. PMID 312296.

External links[edit]

Adenosylhomocysteinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Further reading[edit]

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.

This article incorporates text from the public domain Pfam and InterPro: IPR000043

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase
LEUCINE→	3-Hydroxybutyryl-CoA dehydrogenase Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase HMG-CoA lyase HMG-CoA reductase Isovaleryl coenzyme A dehydrogenase α-Ketoisocaproate dioxygenase Leucine 2,3-aminomutase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase (See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase)
TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase
PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase Creatine kinase
alanine→	Alanine transaminase
cysteine→	D-cysteine desulfhydrase
threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate

HISTIDINE→	Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase
proline→	Proline oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1
arginine→	Ornithine aminotransferase Ornithine decarboxylase Agmatinase
→alpha-ketoglutarate→TCA	Glutamate dehydrogenase
Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione synthetase Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase
ISOLEUCINE→	Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
METHIONINE→	generation of homocysteine: Methionine adenosyltransferase Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase
THREONINE→	Threonine aldolase
→succinyl-CoA→TCA	Propionyl-CoA carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate

PHENYLALANINE→tyrosine→

tyrosine→melanin: Tyrosinase

G→oxaloacetate

asparagine→aspartate→

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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