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.