Carboxylesterases hydrolytic reactions

Esters, amides, hydrazides, and carbamates can all be metabolized by hydrolysis. The enzymes, which catalyze these hydrolytic reactions, carboxylesterases and amidases, are usually found in the cytosol, but microsomal esterases and amidases have been described and some are also found in the plasma. The various enzymes have different substrate specificities, but carboxylesterases have amidase activity and amidases have esterase activity. The two apparently different activities may therefore be part of the same overall activity. 

The hydrolytic reactions are mostly catalyzed by carboxylesterases although other names may be used for the enzymes involved depending on the substrates... 

Ester and amide hydrolytic reactions are mediated principally by carboxylesterases (GES), though other esterases play a role in the hydrolysis of a limited number of esters. Other key biotransformations include oxidations and conjugation reactions. 

The hydrolysis of esters by esterases and of amides by amidases constitutes one of the most common enzymatic reactions of xenobiotics in humans and other animal species. Because both the number of enzymes involved in hydrolytic attack and the number of substrates for them is large, it is not surprising to observe interspecific differences in the disposition of xenobiotics due to variations in these enzymes. In mammals the presence of carboxylesterase that hydrolyzes malathion but is generally absent in insects explains the remarkable selectivity of this insecticide. As with esters, wide differences exist between species in the rates of hydrolysis of various amides in vivo. Fluoracetamide is less toxic to mice than to the American cockroach. This is explained by the faster release of the toxic fluoroacetate in insects as compared with mice. The insecticide dimethoate is susceptible to the attack of both esterases and amidases, yielding nontoxic products. In the rat and mouse, both reactions occur, whereas sheep liver contains only the amidases and that of guinea pig only the esterase. The relative rates of these degradative enzymes in insects are very low as compared with those of mammals, however, and this correlates well with the high selectivity of dimethoate. 

There is little doubt that lipases claimed to be non-regioselective display activity towards the secondary alcoholic mid-position of TAGs, but this may well be different when it comes to re-esterification of that position with fatty acids or their derivatives. Interestingly enough, there is a recent report on conversion of a carboxylesterase into a triacylglycerol lipase by random mutation (Reyes-Duarto et al., 2005). The hydrolytic enzyme was observed to display preference for the sn-2 position of triacylglycerols in an ethanolysis reaction. 

In addition to the hydrolysis of cocaine, the purified human liver cocaine methyl ester hydrolase also catalyzed the ethyl transesterification of cocaine with ethanol to form cocaethylene and methanol as shown in figure 1 (Dean et al. 1991 Brzezinski et al. 1994). Both the hydrolytic and the ethyl transesterification reactions increased as the two activities were analyzed in protein fractions obtained during the enzyme purifi-cation by column chromatography. This suggests that the separate activities are catalyzed by the same enzyme. The Km values for cocaine and ethanol of the purified enzyme at pH 7.3 were 116 M and 43 mM, respectively. The carboxylesterase also catalyzes the formation of ethyloleate from oleic acid and ethanol (Tsujita and Okuda 1992 Brzezinski et al. 1994). Other hydrolases or ester transferases have been reported to catalyze similar substrate "ethylation" reactions. 

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