Browse by author
Lookup NU author(s): Dr Christopher Jewell,
Dr Elaine Mutch,
Professor Faith Williams
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Human liver has numerous hydrolytic enzymes involved in metabolism of endogenous and exogenous esters. Of these enzymes, carboxylesterases (EC 188.8.131.52) 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.
Author(s): Jewell C, Bennett P, Mutch E, Ackermann C, Williams FM
Publication type: Article
Publication status: Published
Journal: Biochemical Pharmacology
ISSN (print): 0006-2952
ISSN (electronic): 1873-2968
Altmetrics provided by Altmetric