CESfamilien

CESfamilien refers to the gene family of carboxylesterases, a group of hydrolytic enzymes that catalyze the cleavage of ester bonds in a wide range of substrates. These enzymes are found throughout the animal kingdom, including vertebrates and invertebrates, and show substantial diversification among species. In humans, the family includes several members commonly designated CES1, CES2, CES3, CES4, CES5 and CES6, among others, with distinct tissue distributions and substrate preferences.

Biochemical features: Carboxylesterases typically adopt an alpha/beta hydrolase fold and employ a catalytic triad consisting of serine, histidine and an acidic residue (glutamate or aspartate). They can be cytosolic or associated with cellular membranes or the endoplasmic reticulum, and their activities can be modulated by glycosylation and other post-translational modifications.

Functions: They hydrolyze a broad range of esters and amides, contributing to lipid metabolism and detoxification of xenobiotics, including many pharmaceutical prodrugs and pesticides. In pharmacology, CES1 and CES2 play major roles in activating or inactivating ester prodrugs. For example, CES1 is known to activate oseltamivir; polymorphisms or altered expression can affect drug response and toxicity.

Genomics and evolution: The CES gene family has undergone lineage-specific expansions, resulting in multiple paralogs in many species. In humans, multiple CES genes exist on different chromosomes, with CES1 and CES2 being among the most studied due to their functional significance in drug metabolism.

Research and applications: CES enzymes are studied for understanding drug disposition, toxicity risk, and the design of prodrugs. They are also explored as biocatalysts for stereoselective synthesis and the bioremediation of ester-containing pollutants.