Glucuronidation of hydroxylated polychlorinated biphenyls (PCBs)

Nilufer Tampal; Hans-Joachim Lehmler; Parvaneh Espandiari; Tina Malmberg; Larry W Robertson

doi:10.1021/tx0200212

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Glucuronidation of hydroxylated polychlorinated biphenyls (PCBs)

Journal article

Peer reviewed

Glucuronidation of hydroxylated polychlorinated biphenyls (PCBs)

Nilufer Tampal, Hans-Joachim Lehmler, Parvaneh Espandiari, Tina Malmberg and Larry W Robertson

Chemical research in toxicology, Vol.15(10), pp.1259-1266

10/2002

DOI: 10.1021/tx0200212

PMID: 12387623

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Abstract

Polychlorinated biphenyls (PCBs) may be metabolized to hydroxylated compounds. While many of these metabolites are further converted to either the glucuronic acid or the sulfate conjugates by phase II enzymes, which facilitates their excretion, some hydroxylated PCBs persist in the body. This may reflect their inability to be conjugated. A possible role of uridine diphosphate glucuronosyl transferase (UGT) in the elimination of hydroxylated metabolites of PCBs was therefore investigated. Glucuronidation studies of PCB metabolites included ones which are eliminated with relative ease and also ones which are reported to be retained in blood. Liver microsomes, prepared from male Wistar rats treated by intraperitoneal injections of phenobarbital for 3 days (400 micromol/kg/day), were used as the source of UGT. Enzyme kinetics (V(max) and K(m)) were determined for each of the metabolites. The efficiency of glucuronidation (V(max)/K(m)) was found to vary from <3 to 116 microL/min/mg and was dependent on the structure of the metabolites. Substitution of chlorine atoms on the nonhydroxylated ring greatly lowered the V(max) of the enzyme, with substitution in the meta and para positions being least favorable for enzyme activity. Steric hindrance around the hydroxyl group by chlorines on adjacent carbon atoms did not play a major role. A weak relationship between the calculated dihedral angle (planarity), pK(a), log D, and enzyme activity was determined (r(2) < 0.5). However, a stronger relationship for the surface area and surface volume of the molecule was observed (r(2) >or= 0.5). This study explains in part why some PCB metabolites persist in the body.

Glucuronosyltransferase - pharmacology

Uridine Diphosphate Glucuronic Acid - chemistry

Rats, Wistar

Environmental Pollutants - pharmacokinetics

Injections, Intraperitoneal

Rats

Male

Environmental Pollutants - metabolism

Polychlorinated Biphenyls - metabolism

Animals

Polychlorinated Biphenyls - chemistry

Polychlorinated Biphenyls - pharmacokinetics

Microsomes, Liver - enzymology

Molecular Structure

Details

Title: Subtitle: Glucuronidation of hydroxylated polychlorinated biphenyls (PCBs)
Creators: Nilufer Tampal - Graduate Center for Toxicology, University of Kentucky Chandler Medical Center, 306 Health Sciences Research Building, Lexington, Kentucky 40536-0305, USA
Hans-Joachim Lehmler
Parvaneh Espandiari
Tina Malmberg
Larry W Robertson
Resource Type: Journal article
Publication Details: Chemical research in toxicology, Vol.15(10), pp.1259-1266
DOI: 10.1021/tx0200212
PMID: 12387623
NLM abbreviation: Chem Res Toxicol
ISSN: 0893-228X
eISSN: 1520-5010
Publisher: United States
Grant note: P42 ES 07380 / NIEHS NIH HHS
Language: English
Date published: 10/2002
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984001093602771

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