Hepatic esterase activity

Rats fed alfalfa, bentonite and corn oil supplements were killed at the end of the growth trials and livers were removed for measurement of non-specific hepatic esterase activity (EC 3.1.1.1 Dabich et al. (1968)). Specific activity was expressed as ymoles a-napthol produced/minute/mg protein with protein determined according to Lowry et al. (1951). 

The role of dietary fats in alleviation of T-2 toxicosis is not easily explained. No evidence was gathered to show that dietary fats altered T-2 metabolism. Hepatic esterase activities were unchanged and the degree of unsaturation of lipid had no effect on feed refusal. The fatty acid composition of dietary oils has been shown to alter mixed frunction oxidase activity in rats (Gefferth and Blakovits, 1977) and it was thought that this might influence T-2 toxin metabolism. 

M., Ito, Y., Sugiura, M., Comparative study of human intestinal and hepatic esterases as related to enzymatic properties and hydrolyzing activity for ester-type drugs, Jpn. J. Pharmacol. 

Orally administered oseltamivir phosphate is rapidly absorbed and converted by hepatic esterases to oseltamivir carboxylate. Approximately 80% of an oral dose reaches the systemic circulation as oseltamivir carboxylate, with peak plasma concentrations achieved within 2.5 to 5 hours. The plasma elimination half-life of oseltamivir carboxylate is 7 to 9 hours. Elimination of the parent drug and its active metabolite occurs primarily by active tubular secretion and glomerular filtration. 

Valganciclovir is a monovalyl ester prodrug that is rapidly hydrolyzed to the active compound ganciclovir (see Ganciclovir) by intestinal and hepatic esterases when administered orally. 

The activity of hepatic esterase (EC 3.1.1.1.) was not significantly affected by dietary alfalfa, bentonite or corn oil. Supplementation of the control diet with 3 yg/g of T-2 toxin also failed to induce this enzyme. 

T-2 toxin is believed to undergo selective C-4 deacetylation by hepatic microsomal carboxyesterase to yield HT-2 toxin (Ohta et al., 1977 Otta et al., 1978). Further metabolism by the same enzyme leads to the stepwise conversion of HT-2 toxin to the more polar metabolites 4-deactylneosolaniol and T-2 tetraol (Yoshizawa et al., 1980a). The lack of effect of T-2 toxin on the activity of heaptic esterase may be due to the non-specific nature of this enzyme. The low dose of toxin may not have been enough to cause substrate induction of the enzyme. The lack of effect of additives on the activity of hepatic esterase adds support to the concept that they do not alleviate T-2 toxicosis by promoting catabolism of the toxin. 

Hepatic microsomes contain a number of enzymes possessing esterase activity. For example, meperidine is hydrolysed by a system found in microsomes but not in plasma ... 

It was reported that the distribution and activities of esterases that catalyze pyrethroid metabolism using several human and rat tissues, including small intestine, liver, and serum, were examined [30]. The major esterase in human intestine was hCE2. //c/n.v-Permethrin was effectively hydrolyzed by pooled human intestinal microsomes (five individuals), while deltamethrin and bioresmethrin were not. This result correlated well with the substrate specificity of recombinant hCE2. In contrast, pooled rat intestinal microsomes (five animals) hydrolyzed trans-permethrin 4.5 times slower than the human intestinal microsomes. Furthermore, pooled samples of cytosol from human or rat liver were ca. half as hydrolytically active as the corresponding microsome fraction toward pyrethroids however, the cytosolic fractions had significant amounts (ca. 40%) of the total hydrolytic activity. Moreover, a sixfold interindividual variation in hCEl protein expression in human hepatic cytosols was observed. 

The intracellular localization of carboxylesterases is predominantly microsomal, the esterases being localized in the endoplasmic reticulum [73] [79] [93], They are either free in the lumen or loosely bound to the inner aspect of the membrane. The carboxylesterases in liver mitochondria are essentially identical to those of the microsomal fraction. In contrast, carboxylesterases of liver lysosomes are different, their isoelectric point being in the acidic range. Carboxylesterase activity is also found in the cytosolic fraction of liver and kidney. It has been suggested that cytosolic carboxylesterases are mere contaminants of the microsomal enzymes, but there is evidence that soluble esterases do not necessarily originate from the endoplasmic reticulum [94], In guinea pig liver, a specific cytosolic esterase has been identified that is capable of hydrolyzing acetylsalicylate and that differs from the microsomal enzyme. Also, microsomal and cytosolic enzymes have different electrophoretic properties [77]. Cytosolic and microsomal esterases in rat small intestinal mucosa are clearly different enzymes, since they hydrolyze rac-oxazepam acetate with opposite enantioselectivity [95], Consequently, studies of hydrolysis in hepatocytes reflect more closely the in vivo hepatic hydrolysis than subcellular fractions, since cytosolic and microsomal esterases can act in parallel. 

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