Understanding Human Carboxylesterase 2

Dissertation presented to obtain the Ph.D degree in Engineering and Technology Sciences, Biotechnology

The first barrier oral drugs and prodrugs encounter prior to reaching an organism’s systemic circulation is the gastrointestinal (GI) tract, specifically the intestine, which is the primary section for absorption. Therefore, it is fundamental to understand the permeability of the therapeutic agent as well as its potential metabolism by human enterocytes, since biotransformation may result in the inactivation of the therapeutic agent or, to the contrary, in the formation of more therapeutically active metabolites. Carboxylesterases (CESs), phase I metabolising enzymes, are important in the metabolism of several drugs and prodrugs with amide, ester, or thioester functional groups. After cytochrome (CYP) P450s and UDP-glucuronosyltransferases (UGTs), CESs are the most relevant enzymes for the metabolism of therapeutic agents.(...)