Humans carboxylesterases

Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B (2006) Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319 1477-1484... 

Ross MK, Crow JA (2007) Human carboxylesterases and their role in xenobiotic and endobi-otic metabolism. J Biochem Mol Toxicol 21 187-196... 

Xu G, Zhang W, Ma MK, McLeod FIL (2002) Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan. Clin Cancer Res 8 2605-2611... 

Yang D, Pearce RE, Wang X, Gaedigk R, Wan YJ, Yan B (2009) Human carboxylesterases HCE1 and HCE2 ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin. Biochem Pharmacol 77 238-247... 

Imai T. Human carboxylesterase isozymes catalytic properties and rational drug design. Drug Metab Pharmacokinet 2006 21 (3) 173—185. 

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). 

Byun, H.M., Choi, S.H., Laird, P.W., Trinh, B., Siddiqui, M.A., Marquez, V.E. and Yang, A.S. (2008) 2 -Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine a novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1. Cancer Letters, 266, 238-248. 

Several human carboxylesterases have been cloned, sequenced and expressed. These human carboxylesterases are important in the hydrolysis of certain pesticides such as the pyrethroids. In certain strains of insects that are resistant to malathion, the resistance mechanism is associated with a higher level of a carboxylesterase, which detoxifies malathion (Figure 10.10D). 

Wierdl M, Tsurkan L, Hyatt JL, et al. An improved human carboxylesterase for enzyme/ prodrug therapy with CPT-11. Cancer Gene Ther 2008 15(3) 183—92. 

Redinbo, M., Bencharit, S. and Potters, P. (2003), Human carboxylesterase 1 from drug metabolism to drug discovery, Biochem. Soc. Trans., 31, 620-624. 

Shibata, R, Takagi, Y, Kitajima, M., Kuroda, T., and Omura, T., Molecular cloning and characterization of a human carboxylesterase gene. Genomics, 17, 76, 1993. 

Vistoli G, Pedretti A, Mazzolari A, Testa B (2010) In silico prediction of human carboxylesterase-1 (hCESl) metabolism combining docking analysis and MD simulations. Bioorg Med Chem 18 320-329... 

CES1/CES2 hCE-1 and hCE-2 belong to these two classes of human carboxylesterases... 

Fleming, C D., Edwards, C.E., Kirby, S.D., et al., 2007. Crystal structure of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun. Biochemistry 46,5063-5071. 

Hemmert, A.C., Otto, T.C., Wierdl, M., et al., 2010. Human carboxylesterase 1 stereoselectively binds the nerve agent cyclosarin and spontaneously hydrolyzes the nerve agent sarin. Mol. Pharmacol. 77,508-516. 

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