Carboxylesterase superfamily

The carboxylesterase superfamily catalyzes the hydrolysis of ester- and amide-containing compounds. These enzymes are found in both the ER and cytosol of many cell types and are involved in detoxification or metabolic activation of drugs, environmental toxins, and carcinogens. Car-boxylesterases also catalyze the activation of prodrugs to their respective free acids. For example, the prodrug and cancer chemotherapeutic agent irinotecan is bioactivated by plasma and intracellular carboxylesterases to the potent topoisomerase inhibitor SN-38. 

Figure 12 Phylogenetic tree of the carboxylesterase superfamily. (Adapted from Ref. 43.)...

In analogy to other enzyme systems, the superfamily of carboxylesterases has been divided into families and subfamilies based on sequence homology (Table 2.7) [79], The major family, CES 1, all exhibit >60% homology with human carboxylesterase HU 1. This family is divided into subfamilies, namely CES 1A, IB, and 1C. As shown in Table 2.7, the enzyme CES 1A1 includes the major forms of human carboxylesterases (>99.5% homology). 

Ubiquitous glycosylated carboxylesterases (CarbE, EC 3.1.1.1), formerly named ali-esterases, are B-esterases belonging to the multigene enzyme superfamily of a/P hydrolases (Hosokawa and Satoh, 2006 Satoh and Hosokawa, 2006). In principle this class of isozymes plays a major role in pharmacokinetics by hydrolytic biotransformation of exogenous ester-drugs and ester-prodrugs. However, their physiological fimction still remains unclear (Satoh and Hosokawa, 2006). 

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