Perfluorodecanoic acid noncompetitively inhibits the peroxisomal enzymes enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase

T Borges; H P Glauert; L W Robertson

doi:10.1006/taap.1993.1003

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Perfluorodecanoic acid noncompetitively inhibits the peroxisomal enzymes enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase

Journal article

Peer reviewed

Perfluorodecanoic acid noncompetitively inhibits the peroxisomal enzymes enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase

T Borges, H P Glauert and L W Robertson

Toxicology and applied pharmacology, Vol.118(1), pp.8-15

01/1993

DOI: 10.1006/taap.1993.1003

PMID: 8430427

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Abstract

The mechanisms of the inhibition of hepatic peroxisomal beta-oxidation by the peroxisome proliferator PFDA3 were studied. Female Sprague Dawley rats were given a single ip injection of either 0, 10, or 40 mg/kg PFDA or were placed on a diet supplemented with the peroxisome proliferator ciprofibrate (0.01%). After 2 weeks, the rats were killed, and hepatic peroxisomes were isolated by discontinuous sucrose gradient centrifugation. Treatment of rats with either PFDA or ciprofibrate increased the individual activities of each of the enzymes in the peroxisomal beta-oxidation pathway. Similarly, treatment of rats with ciprofibrate greatly increased total peroxisomal beta-oxidation, but peroxisomal beta-oxidation was slightly decreased in rats treated with 40 mg/kg PFDA. In vitro inhibition studies found that PFDA was a noncompetitive and reversible inhibitor of both the activities of the peroxisomal bifunctional protein, namely enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. The Ki of the inhibition was approximately 5 microM. PFDA only slightly inhibited the activity of peroxisomal fatty acyl CoA oxidase, and did not inhibit peroxisomal thiolase activity. We therefore conclude that PFDA inhibits peroxisomal beta-oxidation by noncompetitively inhibiting the peroxisomal bifunctional enzyme.

Microbodies - enzymology

3-Hydroxyacyl CoA Dehydrogenases - antagonists & inhibitors

Decanoic Acids - pharmacology

Body Weight - drug effects

Microbodies - drug effects

Rats

Fluorocarbons - pharmacology

Rats, Sprague-Dawley

Animals

Enoyl-CoA Hydratase - antagonists & inhibitors

Liver - drug effects

Female

Kinetics

In Vitro Techniques

Details

Title: Subtitle: Perfluorodecanoic acid noncompetitively inhibits the peroxisomal enzymes enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase
Creators: T Borges - Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054
H P Glauert
L W Robertson
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.118(1), pp.8-15
Publisher: United States
DOI: 10.1006/taap.1993.1003
PMID: 8430427
ISSN: 0041-008X
eISSN: 1096-0333
Grant note: CA43719 / NCI NIH HHS CA01688 / NCI NIH HHS ES07266 / NIEHS NIH HHS
Language: English
Date published: 01/1993
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002586902771

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