Reactome: A Curated Pathway Database

Defective MUT does not isomerise L-MM-CoA to SUCC-CoA (R-HSA-3322971)

Species Homo sapiens

Summation

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).

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Additional Information
Compartment mitochondrial matrix
Components of this entry
Input entries
Diseases
Name Identifier Synonyms
methylmalonic acidemia 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]
Literature References
pubMedId Title Journal Year
2567699 Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction Genomics 1989
16281286 Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype Hum. Mutat. 2006
1970180 Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia Proc. Natl. Acad. Sci. U.S.A. 1990
1977311 Heterozygous mutations at the mut locus in fibroblasts with mut0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning Am. J. Hum. Genet. 1990
1670635 Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation J. Clin. Invest. 1991
8990001 Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations Hum. Mutat. 1997
7909321 Cloning and expression of mutations demonstrating intragenic complementation in mut0 methylmalonic aciduria J. Clin. Invest. 1994
11528502 N219Y, a new frequent mutation among mut(degree) forms of methylmalonic acidemia in Caucasian patients Eur. J. Hum. Genet. 2001
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 Hum. Mutat. 2005
11350191 Mutation analysis of the MCM gene in Israeli patients with mut(0) disease Mol. Genet. Metab. 2001
16451139 Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria Clin. Genet. 2006