Defective AHCY does not hydrolyse AdoHcy

Stable Identifier
R-HSA-5579084
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Adenosylhomocysteinase (AHCY) is a tetrameric, NAD+-bound, cytosolic protein that regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolysing the feedback inhibitor adenosylhomocysteine (AdoHcy) to homocysteine (HCYS) and adenosine (Ade-Rib) (Turner et al. 1998, Yang et al. 2003). Defects in AHCY cause Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD; MIM:613752), a metabolic disorder characterised by hypermethioninemia associated with failure to thrive, psychomotor retardation, facial dysmorphism with abnormal hair and teeth and myocardiopathy. Gene analysis revealed two mutations that can cause HMAHCHD; W112* and Y143C (Baric et al. 2004).

Literature References
PubMed ID Title Journal Year
9586999 Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength

Turner, MA, Yuan, CS, Borchardt, RT, Hershfield, MS, Smith, GD, Howell, PL

Nat. Struct. Biol. 1998
12590576 Catalytic strategy of S-adenosyl-L-homocysteine hydrolase: transition-state stabilization and the avoidance of abortive reactions

Yang, X, Hu, Y, Yin, DH, Turner, MA, Wang, M, Borchardt, RT, Howell, PL, Kuczera, K, Schowen, RL

Biochemistry 2003
15024124 S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism

Baric, I, Fumic, K, Glenn, B, Cuk, M, Schulze, A, Finkelstein, JD, James, SJ, Mejaski-Bosnjak, V, Pazanin, L, Pogribny, IP, Rados, M, Sarnavka, V, Scukanec-Spoljar, M, Allen, RH, Stabler, S, Uzelac, L, Vugrek, O, Wagner, C, Zeisel, S, Mudd, SH

Proc. Natl. Acad. Sci. U.S.A. 2004
Participants
Participates
Catalyst Activity

adenosylhomocysteinase activity of AHCY mutants:NAD+ tetramer [cytosol]

Normal reaction
Functional status

Loss of function of AHCY mutants:NAD+ tetramer [cytosol]

Status
Disease
Name Identifier Synonyms
hypermethioninemia DOID:0050544 HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
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