4epimerasi

4-epimerase, or 4epimerase, is an enzyme class that catalyzes the stereochemical inversion at the fourth carbon (C-4) of a sugar molecule, producing a 4-epimer. This type of reaction commonly occurs on sugar nucleotides, such as UDP-glucose and UDP-galactose, but can also affect other sugars. The process is often reversible and may involve cofactors that facilitate oxidation and reduction at C-4.

The best-known member of this group is UDP-glucose 4-epimerase (GALE; EC 5.1.3.2). GALE interconverts UDP-glucose and UDP-galactose, a key step in the Leloir pathway of galactose metabolism. In many organisms, the enzyme is NAD+-dependent and operates via a two-step mechanism that oxidizes C-4 to a 4-keto intermediate and then reduces it to the inverted configuration. This epimerization provides UDP-galactose for glycosylation reactions and polysaccharide biosynthesis, including lactose synthesis in mammals, where UDP-galactose serves as a donor for lactose synthase.

Biological distribution and importance vary by organism. GALE is found in bacteria, plants, and animals, reflecting a widespread need to balance UDP-glucose and UDP-galactose pools for carbohydrate biosynthesis and modification of glycoproteins and glycolipids. In humans, GALE deficiency can contribute to a galactosemia-like phenotype (GALE deficiency), with severity ranging from mild to clinically significant, underscoring the enzyme’s role in galactose handling and glycan biosynthesis.

Other 4-epimerases exist in nature, acting on different substrates and participating in diverse metabolic pathways. They are typically categorized within the broader family of epimerases, enzymes that alter stereochemistry at specific carbon centers in sugars.