Mutase

Mutase is an enzyme that catalyzes intramolecular transfer of a functional group, producing structural isomers by repositioning parts of the same molecule. In the Enzyme Commission (EC) classification, mutases are categorized as isomerases (EC 5), specifically within the subgroups that perform intramolecular group transfer. Rather than altering oxidation state or forming new bonds with external substrates, mutases rearrange the molecule's connectivity, often preparing substrates for subsequent metabolic steps.

Mutases employ a variety of mechanisms and cofactors. Some operate via a covalent enzyme intermediate, such as phosphoglucomutase and phosphoglycerate mutase, which exchange a phosphate on the substrate through a phosphorylated amino acid in the active site. Others are cofactor-dependent, using cofactors like adenosylcobalamin (vitamin B12) to support radical rearrangements, as seen in methylmalonyl-CoA mutase. Additional mutases rely on metal ions or other cofactors to facilitate group transfer within the molecule.

Prominent examples include methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in propionate catabolism, linking propionate metabolism to the tricarboxylic acid cycle. Phosphoglucomutase catalyzes the interconversion between glucose-1-phosphate and glucose-6-phosphate, a key step in carbohydrate metabolism and glycogen biosynthesis. Phosphoglycerate mutase participates in glycolysis, shifting the phosphate between adjacent carbons of 3-phosphoglycerate to form 2-phosphoglycerate. Some bacteria use isopropylmalate mutase in leucine biosynthesis to rearrange carbon skeletons within the pathway.

Mutases are essential for various metabolic routes, and defects in mutase enzymes can lead to metabolic disorders, notably methylmalonic acidemia from methylmalonyl-CoA mutase deficiency. Beyond basic biochemistry, mutases are studied for metabolic engineering and the production of isomerically distinct compounds in industrial microbiology.