Reactome | MMAA:MUT binds AdoCbl

MMAA:MUT binds AdoCbl

Stable Identifier

R-HSA-3159259

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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Methylmalonyl-CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor and catalyses interchange of a carbonyl-CoA group and a hydrogen atom in conversion of methymalonyl-CoA to form succinyl-CoA, a precursor for the citric acid cycle. MUT has a homodimeric structure and is located in the mitochondrial matrix. Defects in MUT cause methylmalonic aciduria type mut (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006).

Methylmalonic aciduria type A protein (MMAA) (Dobson et al. 2002) is thought to act as a chaperone to MUT and is suggested to play a dual role with regards to MUT protection and reactivation.

Defects in MMAA cause methylmalonic aciduria type cblA (MMAA 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 (Dobson et al. 2002, Lerner-Ellis et al. 2004).

Literature References

PubMed ID	Title	Journal	Year
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
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