Defective AHCY does not hydrolyse AdoHcy

Stable Identifier
R-HSA-5579084
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Defective AHCY does not hydrolyse AdoHcy
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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
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
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
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
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Catalyst Activity

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

Physical Entity
AHCY mutants:NAD+ tetramer [cytosol] (Homo sapiens)
Activity
adenosylhomocysteinase activity (GO:0004013)
Normal reaction
AHCY:NAD+ tetramer hydrolyses AdoHcy (Homo sapiens)
Functional status

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

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
hypermethioninemia DOID:0050544 HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
Cross References
Mondo
Authored
Jassal, B  (2014-06-06)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-06-06)
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