Epimerase

An epimerase is an enzyme that catalyzes epimerization, the inversion of configuration at a single stereogenic center in a molecule. Most well-characterized epimerases act on carbohydrates, especially sugar nucleotides such as UDP- or dTDP-sugars, but the term can apply to other substrates. Epimerases are classified as isomerases (EC 5.1.3) and usually catalyze reversible reactions critical for the biosynthesis of polysaccharides, glycoproteins, and cell-wall components.

Mechanistically, epimerases use two broad strategies. Redox-dependent epimerases oxidize a carbon center to form a transient 4-keto (or equivalent) intermediate, then reduce it from the opposite face, often requiring NAD+ as a cofactor. Non-oxidative epimerases employ general acid-base catalysis, with active-site residues that abstract and donate protons to invert configuration without changing oxidation state. Some enzymes proceed through concerted proton transfers or conformational changes to enable inversion.

Prominent examples include UDP-glucose 4-epimerase (GALE), which interconverts UDP-glucose and UDP-galactose in the Leloir pathway, and dTDP-4-keto-6-deoxyglucose 3,5-epimerase (RmlC), a step in dTDP-L-rhamnose biosynthesis in bacteria. Other epimerases act on UDP-N-acetylglucosamine and related substrates in capsule and glycoprotein biosynthesis.

Biological importance depends on context. In humans, GALE participates in nucleotide-sugar interconversion required for glycosylation; defects lead to metabolic disorders. In microbes, epimerases shape cell wall and surface polysaccharides and can influence virulence, making them potential drug targets and biotechnological tools for producing rare sugars.