Human liver carboxylesterase 1 structure, polymorphism and its role in drug and prodrug activation and metabolism

Abstract

The human carboxylesterase 1 or CES1 is an enzyme predominantly expressed in the liver where numerous hydrolytic reactions take place. It is believed that this enzyme is responsible for approximately 80% of hydrolytic activity in the liver and leaves the rest of 20% to its counterpart enzyme, human carboxylesterase 2 (CES2). CES1 plays a critical role in hydrolysis of numerous compounds which contain ester- and amide-bonds, including drugs, prodrugs, endobiotics, and xenobiotics. Owing to its significant role, extensive studies have been carried out to investigate its gene structure and polymorphisms, protein structure and function as well as many other aspects. The present review highlights the importance of the structure of CES1 in regard to its function and catalytic activity. Additionally, it was found that CES1 catalytic activity can be influenced by variations or SNPs in DNA coding region, promoter region as well as 5’ untranslated region of CES1. These alterations in the catalytic activity of an enzyme have been shown to associate with clinical outcomes. Therefore, polymorphisms related to functional activity of CES1 in the hydrolysis of drugs and prodrugs are also discussed.