Defective MUT does not isomerise L-MM-CoA to SUCC-CoA

Stable Identifier
Reaction [transition]
Homo sapiens
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Methylmalonyl CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor catalyzes interchange of a carbonylCoA group and a hydrogen atom in conversion of methylmalonyl 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, mut type (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006). Patients with no residual MUT activity are defined as MMA mut(0); those with some residual MUT activity are defined as MMA mut(-). Mutations causing MMA mut(0) type of disorder include Q17*, W105R, A378E, R93H, G623R, G703R, N219Y, R108C and G215S (Ledley et al. 1990, Jansen & Ledley 1990, Raff et al 1991, Ledley & Rosenblatt 1997, Qureshi et al. 1994, Acquaviva et al. 2001, Acquaviva et al. 2005, Berger et al. 2001, Worgan et al. 2006, Cavicchi et al. 2006).
Literature References
PubMed ID Title Journal Year
16451139 Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria

la Marca, G, Poggi, GM, Morrone, A, Zammarchi, E, Funghini, S, Pasquini, E, Donati, MA, Ciani, F, Cavicchi, C, Malvagia, S

Clin. Genet. 2006
15643616 Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene

Koskas, T, Pereira, S, Elion, J, Callebaut, I, Porquet, D, Acquaviva, C, Benoist, JF

Hum. Mutat. 2005
1970180 Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia

Jansen, R, Rosenberg, LE, Nham, SU, Ledley, FD, Fenton, WA

Proc. Natl. Acad. Sci. U.S.A. 1990
11350191 Mutation analysis of the MCM gene in Israeli patients with mut(0) disease

Elpeleg, ON, Anikster, Y, Berger, I, Joseph, A, Bar-Meir, M, Baumgartner, ER, Shaag, A

Mol. Genet. Metab. 2001
8990001 Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations

Ledley, FD, Rosenblatt, DS

Hum. Mutat. 1997
1670635 Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation

Jansen, R, Crane, AM, Raff, ML, Ledley, FD, Rosenblatt, DS

J. Clin. Invest. 1991
1977311 Heterozygous mutations at the mut locus in fibroblasts with mut0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning

Jansen, R, Ledley, FD

Am. J. Hum. Genet. 1990
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
11528502 N219Y, a new frequent mutation among mut(degree) forms of methylmalonic acidemia in Caucasian patients

Porquet, D, Ogier de Baulny, H, Touati, G, Acquaviva, C, Elion, J, Callebaut, I, Aydin, A, Guffon, N, Benoist, JF

Eur. J. Hum. Genet. 2001
7909321 Cloning and expression of mutations demonstrating intragenic complementation in mut0 methylmalonic aciduria

Matiaszuk, NV, Crane, AM, Qureshi, AA, Ledley, FD, Rezvani, I, Rosenblatt, DS

J. Clin. Invest. 1994
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
Catalyst Activity

methylmalonyl-CoA mutase activity of 2xMMAA:mutant MUT:AdoCbl [mitochondrial matrix]

Normal reaction
Functional status

Loss of function of 2xMMAA:mutant MUT:AdoCbl [mitochondrial matrix]

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