Lungs carboxylesterases

B. Ab, T. Imamura, Characteristics Of Rat Lung Carboxylesterases/Amidases , Proc. West. Pharmacol. Soc. 1985, 28, 319-322 B. Ab, S. Kaur, Mammaban Tissue Acet-ylsabcybc Acid Esterase(s) Identification, Distribution and Discrimination from Other Esterases , J. Pharmacol. Exp. Then 1983, 226, 589 - 594. 

Cauxin is markedly different from previously reported mammalian CESs in term of urinary excretion. Other mammalian CESs comprise multigene families, and CES isozymes are highly and ubiquitously expressed in tissues such as the brain, liver, kidney, lung, and small intestine (Satoh and Hosokawa 1998). Our work on cauxin was the first description of a carboxylesterase excreted in urine. 

Carboxylesterases (EC 3.1.1.1) can be detected in most mammalian tissues. Besides organs with high carboxylesterase activity such as liver, kidney, and small intestine, esterase activity is present, e.g., in the brain, nasal mucosa, lung, testicle, and saliva. Compared to rat plasma, human plasma contains little carboxylesterase, its esterase activity being essentially due to cholinesterase [61][73][79][89-91],... 

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

Irinotecan, an antineoplastic-prodrug, is widely used for the treatment of colorectal, lung and other cancers, and is one of model pharmaceuticals for personalized medicine. The active metabolite, SN-38, is a topoisomerase I inhibitor generated by hydrolysis of irinotecan by carboxylesterases. SN-38 is subsequently glucuronidated... 

An oral dose of 0.01 mg/kg in humans could be fatal. In animals, soman toxicity varied among species the LD50 values by subcutaneous administration were 20, 28, and 126 pg/kg for rabbits, guinea pigs, and rats, respectively (Maxwell et al. 1988). Exposure to a concentration of 21 mg/m soman caused a large inhibition of the activities of the enzyme carboxylesterase [9016-08-5] in bronchi, lungs, and blood tissues in rats (Aas... 

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