esterases

Esterases are hydrolytic enzymes that catalyze the cleavage of ester bonds in the presence of water, generating an alcohol and a carboxylic acid. They form a diverse group within the serine hydrolase superfamily and are widespread across all domains of life, including animals, plants, microbes, and environmental organisms. Esterases are commonly classified by substrate specificity or EC number, with examples including carboxylesterases (EC 3.1.1.1), cholinesterases such as acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8), and arylesterases (EC 3.1.1.2).

Most esterases are serine hydrolases that utilize a catalytic triad, typically Ser-His-Asp or Ser-His-Glu, to activate a serine nucleophile. The mechanism involves formation of a transient acyl-enzyme intermediate, followed by hydrolysis to release the products and regenerate the free enzyme. Esterases participate in a range of physiological processes, including detoxification of xenobiotics, activation or inactivation of drugs and prodrugs, lipid and ester metabolism, and cellular recycling of esters. In humans, acetylcholinesterase and butyrylcholinesterase play roles in neurotransmission and drug metabolism, while hepatic carboxylesterases contribute to hydrolysis of various endogenous and exogenous esters. Esterases from bacteria, fungi, and plants contribute to degradation pathways and can be harnessed as biocatalysts.

Applications and relevance include drug development, where esterases affect pharmacokinetics and prodrug activation; industrial biocatalysis for selective ester hydrolysis or synthesis; and environmental remediation. Common assay substrates are chromogenic or fluorogenic esters such as p-nitrophenyl esters, used to measure activity and inhibition. Inhibitors include organophosphates and carbamates, which can modulate esterase activity with significant toxicological and therapeutic implications.