Methylmalonyl-CoA mutase

Methylmalonyl-CoA mutase
Methylmalonyl CoA mutase

Rendering based on PDB 2XIJ.
Symbols MUT; MCM
External IDs OMIM609058 MGI97239 HomoloGene20097 GeneCards: MUT Gene
EC number
RNA expression pattern
PBB GE MUT 202959 at tn.png
PBB GE MUT 202960 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4594 17850
Ensembl ENSG00000146085 ENSMUSG00000023921
UniProt P22033 Q3UFU2
RefSeq (mRNA) NM_000255.3 NM_008650.3
RefSeq (protein) NP_000246.2 NP_032676.2
Location (UCSC) Chr 6:
49.4 – 49.43 Mb
Chr 17:
41.07 – 41.1 Mb
PubMed search [1] [2]
methylmalonyl-CoA mutase
EC number
CAS number 9023-90-9
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways. It requires a vitamin B12-derived prosthetic group, adenosylcobalamin, to function.



The substrate of methylmalonyl-CoA mutase, methylmalonyl-CoA, is primarily derived from propionyl-CoA, a substance formed from the catabolism and digestion of isoleucine, valine, threonine, methionine, thymine, cholesterol, or odd-chain fatty acids.

The product of the enzyme, succinyl-CoA, is a key molecule of the TCA cycle.

MCM resides in the mitochondria, where a number of substances, including the branched-chain amino acids isoleucine and valine, as well as methionine, threonine, thymine and odd-chain fatty acids, are metabolized via methylmalonate semialdehyde (MMlSA) or propionyl-CoA (Pr-CoA) to a common compound - methylmalonyl-CoA (MMl-CoA).

Human Genetics

The gene encoding for this enzyme in humans is known as MUT[1].


A deficiency of this enzyme is responsible for an inherited disorder of metabolism, Methylmalonyl-CoA mutase deficiency, which is one of the causes of methylmalonic acidemia.


MUT reaction mechanism begins with homolytic cleavage of AdoB12's C-Co(III) bond, the C and Co atoms each acquire one of the electrons that formed the cleaved electron pair bond. The Co ion, therefore, fluctuates between its Co(III) and Co(II) oxidation states [the two states are spectroscopically distinguishable: Co(III) is red and diamagnetic (no unpaired electrons), whereas Co(II) is yellow and paramagnetic (unpaired electrons)]. Hence, the role of coenzyme B-12 in the catalytic process is that of a reversible free radical generator. The C-Co(III) bond is well suited to this function because it is inherently weak (dissociation energy = 109 kJ/mol) and appears to be further weakened through steric interactions with the enzyme. A homolytic cleavage reaction is unusual in biology; most other biological bond cleavage reactions occur via heterolytic cleavage (in which the electron pair forming the cleaved bond is fully acquired by one of the separating atoms).

MUT's reaction mechanism

See also

  • MMAA
  • MMAB


Further reading

External links