Defective MMAA does not protect MUT

Stable Identifier
R-HSA-3322135
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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Defective MMAA does not protect MUT
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Methylmalonic aciduria type A protein (MMAA) is thought to act as a chaperone to MUT, the enzyme which utilises adenosylcobalamin (AdoCbl) as a cofactor. MMAA is suggested to play a dual role with regards to MUT protection and reactivation. Some AdoCbl-dependent enzymes undergo suicide inactivation after catalysis due to the oxidative inactivation of Cbl. MMAA is thought to play a protective role to prevent MUT being inactivated in this way. Defects in MMAA cause methylmalonic aciduria type cblA (cblA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood. Mutations causing cblA include MMAA Q95*, R145*, Y207C and D87Ifs*11 (Dobson et al. 2002, Lerner-Ellis et al. 2004).
Literature References
PubMed ID Title Journal Year
21138732 Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein

Flores, ME, García-Arellano, H, Takahashi-Íñiguez, T, Trujillo-Roldán, MA

Biochem. Biophys. Res. Commun. 2011
20876572 Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation

Froese, DS, Gravel, RA, Wu, X, Ugochukwu, E, Oppermann, U, Muniz, JR, Kochan, G, Krysztofinska, E, Yue, WW, Gileadi, C

J. Biol. Chem. 2010
12438653 Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements

Dobson, CM, Hudson, T, Doré, C, Gravel, RA, Rosenblatt, DS, Wu, X, Leclerc, D, Wai, T, Wilson, A

Proc. Natl. Acad. Sci. U.S.A. 2002
16866376 Assembly and protection of the radical enzyme, methylmalonyl-CoA mutase, by its chaperone

Padovani, D, Banerjee, R

Biochemistry 2006
16281286 Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype

Niles, K, Worgan, LC, Rosenblatt, DS, Lepage, P, Hofmann, A, Kucic, T, Tirone, JC, Sammak, A, Verner, A

Hum. Mutat. 2006
15523652 Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism

Dobson, CM, Doré, C, Gravel, RA, Rosenblatt, DS, Lepage, P, Leclerc, D, Watkins, D, Wai, T, Tirone, JC, Lerner-Ellis, JP

Hum. Mutat. 2004
2567699 Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction

Jansen, R, Rosenberg, LE, Kalousek, F, Ledley, FD, Fenton, WA

Genomics 1989
Participants
Input
Participates
as an event of
Normal reaction
MMAA:MUT binds AdoCbl (Homo sapiens)
Functional status

Loss of function of 2xMMAA mutants:2xMUT [mitochondrial matrix]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
methylmalonic acidemia DOID:14749 METHYLMALONICACIDURIA DUE TO METHYLMALONIC CoA MUTASE deficiency, METHYLMALONIC ACIDURIA, mut TYPE, METHYLMALONIC ACIDEMIA, cblB TYPE, methylmalonic aciduria mut type, METHYLMALONICACIDURIA, vitamin B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN--cbl B, methylmalonic aciduria cblB type, METHYLMALONIC ACIDURIA DUE TO METHYLMALONYL-CoA MUTASE DEFICIENCY, METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblA TYPE, methylmalonic aciduria, METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblB TYPE, METHYLMALONIC ACIDEMIA, cblA TYPE, METHYLMALONICACIDURIA, vitamin B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN--cbl A
Authored
Jassal, B  (2013-05-03)
Reviewed
Watkins, D  (2013-08-14)
Created
Jassal, B  (2013-05-03)
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