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Inter-individual variability in esterases in human liver

Lookup NU author(s): Dr Christopher Jewell, Phillippa Bennett, Dr Elaine Mutch, Professor Faith Williams

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Abstract

Human liver has numerous hydrolytic enzymes involved in metabolism of endogenous and exogenous esters. Of these enzymes, carboxylesterases (EC 3.1.1.1) form an important group which hydrolyses many diverse ester substrates, including pro-ester drugs. Carboxylesterase activity was investigated in liver subcellular fractions from 22 individuals using the general carboxylesterase substrate phenylvalerate and the homologous series of esters methyl-, ethyl-, propyl-, butyl- and benzylparaben. The intra- and inter-individual variation in phenylvalerate and paraben metabolism was compared. Rates of hydrolysis were higher in microsomal fractions than cytosolic fractions for all compounds. The rate of paraben hydrolysis varied depending on the size of the paraben alcohol leaving group, showing a decrease with increasing leaving group size. Comparisons showed that individuals with high rates of hydrolysis towards methyl paraben also showed high rates of hydrolysis to the other parabens and phenylvalerate. Phenylvalerate as a non-specific carboxylesterase substrate was hydrolysed mainly by hCE1 in human livers and there was good correlation with small alcohol leaving group parabens, suggesting hCE1 involvement. Lower correlations with larger alcohol leaving group parabens are consistent with more hCE2 involvement. ( (C) 2007 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Jewell C, Bennett P, Mutch E, Ackermann C, Williams FM

Publication type: Article

Publication status: Published

Journal: Biochemical Pharmacology

Year: 2007

Volume: 74

Issue: 6

Pages: 932-939

ISSN (print): 0006-2952

ISSN (electronic): 1873-2968

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.bcp.2007.06.022

DOI: 10.1016/j.bcp.2007.06.022


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