The emerging role of human esterases

Area of Science:

• Pharmacology
• Biochemistry
• Drug Metabolism

Background:

• Esterases play a critical role in metabolizing approximately 10% of therapeutic drugs.
• They hydrolyze ester, amide, and thioester bonds, influencing prodrug activation and detoxification.
• While carboxylesterases are well-studied, other esterases are gaining attention for their pharmacological and toxicological significance.

Purpose of the Study:

• To review novel aspects of esterase function in drug metabolism.
• To highlight the roles of specific esterases (AADAC, PON1, BChE, ABHD10) in drug hydrolysis and their clinical implications.
• To emphasize the need for further research into esterase substrate specificity and function.

Main Methods:

• Literature review of esterase involvement in drug metabolism.
• Discussion of specific esterase-drug interactions and their consequences.
• Identification of novel esterases, such as ABHD10, in drug hydrolysis.

Main Results:

• Arylacetamide deacetylase (AADAC) hydrolyzes drugs like flutamide and phenacetin, linked to toxicity.
• Paraoxonase (PON1) and butyrylcholinesterase (BChE) hydrolyze specific drugs (pirocarpine/simvastatin, succinylcholine/bambuterol).
• ABHD10 is identified as a key enzyme for hydrolyzing mycophenolic acid acyl-glucuronide, potentially acting as a detoxification enzyme.

Conclusions:

• Diverse esterases, including newly recognized ones, are involved in drug metabolism with distinct substrate specificities.
• Understanding these esterases is vital for predicting drug efficacy, toxicity, and adverse drug reactions.
• Further research into esterases will advance clinical pharmacotherapy and drug development.