Isomerases

Isomerases are enzymes that catalyze isomerization reactions, converting a molecule into another isomer with the same chemical formula but a different arrangement of atoms. They rearrange bonds, move functional groups, or invert stereochemistry without adding or removing atoms from the substrate. Isomerases are essential for reconfiguring molecules to enable other metabolic steps and to balance metabolic flux.

In enzymology, isomerases form a distinct class (EC 5) within the enzyme commission system. Major subtypes include racemases and epimerases, which invert configurations at one or more stereogenic centers; cis-trans isomerases, which switch geometric isomers; and mutases, which relocate a functional group within the same molecule (intramolecular transfer). Some isomerases may require cofactors such as NAD+, PLP, or metal ions, while others operate without cofactors.

Mechanistically, isomerases often stabilize charged or high-energy intermediates, enabling intramolecular rearrangements. Examples include catalysts that form enediol or enamine-type intermediates or that reposition phosphate or other groups within a sugar or amino acid backbone. The diversity of mechanisms reflects the wide range of substrates and cellular roles.

Notable examples include glucose-6-phosphate isomerase, which interconverts glucose-6-phosphate and fructose-6-phosphate in glycolysis and gluconeogenesis; triose phosphate isomerase, which catalyzes the interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate; phosphoglucomutase, which shifts phosphate between glucose-1-phosphate and glucose-6-phosphate; and alanine racemase, which inverts the configuration of alanine during cell-wall biosynthesis in some bacteria. Isomerases are widespread in metabolism and can be targets for therapeutics and industrial applications.