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

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

Biochemistry 2003
9586999 Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength

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

Nat. Struct. Biol. 1998
15024124 S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism

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

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
Authored
Jassal, B  (2014-06-06)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-06-06)
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