methylmalonyl Coenzyme A mutase; succinyl CoA mutase; methylmalonyl CoA isomerase (MUT, MCM)

Function

• mitochondrial vitamin B12-dependent enzyme
• role in degradation of several amino acids, odd-chain fatty acids & cholesterol via propionyl-CoA to the tricarboxylic acid cycle
• converts methylmalonate (methylmalonyl CoA) to succinate (succinyl CoA) which enters the citric acid cycle
• in humans, methylmalonyl CoA mutase is involved in the metabolism of propionate formed from catabolism of odd-chain fatty acids, cholesterol & the amino acids methionine & isoleucine (via propionyl CoA)
• MCM has different functions in other species

Cofactor: adenosylcobalamin

• the 1st step is the homolytic cleavage of the carbon-cobalt bond in vitamin B12 generating cobalamin (Co+2) & 5'deoxyadenosyl (carbon) radical -CH2*
• the 5'deoxyadenosyl radical -CH2* abstracts a hydrogen atom from the substrate generating 5'deoxyadenosine -(CH3) & a substrate radical which undergoes intramolecular rearrangement to form the product radical
• the product radical then abstracts a hydrogen from 5'deoxyadenosine to form product (succinyl CoA) & the 5'deoxyadenosyl (carbon) radical -CH2* which in turn combines with cobalamin (Co+2) to regenerate adenosylcobalamin

Structure

• homodimer
• belongs to the methylmalonyl-CoA mutase family
• contains 1 B12-binding domain

Compartment

mitochondrial matrix

Pathology

• defects in MUT are the cause of methylmalonicaciduria

More general terms

• mutase
• oligomerizing protein
• mitochondrial protein

Additional terms

• adenosylcobalamin; cobamamide (vitamin B12)
• methylmalonate; methylmalonic acid (MMA)
• succinate; succinic acid
• succinyl coenzyme A

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4594
• UniProt: http://www.uniprot.org/uniprot/P22033.html
• OMIM: https://mirror.omim.org/entry/251000
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4594