Chapter

The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism

Volume 6 of the series Proteins And Cell Regulation pp 209-220

Paraoxonase (PON1) and Organophosphate Toxicity

  • L.G. CostaAffiliated withDept. of Environmental and Occupational Health Sciences, University of WashingtonDept. of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma
  • , T.B. ColeAffiliated withDept. of Environmental and Occupational Health Sciences, University of WashingtonDepts of Genome Sciences and Medicine (Medical Genetics), University of Washington
  • , K.L. JansenAffiliated withDept. of Environmental and Occupational Health Sciences, University of Washington
  • , C.E. FurlongAffiliated withDepts of Genome Sciences and Medicine (Medical Genetics), University of Washington

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Abstract

Paraoxonase (PON1) is a high density lipoprotein-associated enzyme capable of hydrolyzing multiple substrates, including several organophosphorus (OP) insecticides and nerve agents, oxidized lipids and a number of drugs or pro-drugs. Several polymorphisms in the PON1 gene have been described, which have been shown to affect either the catalytic efficiency of hydrolysis or the expression level of the enzyme. Animal studies have shown that PON1 is an important determinant of the toxicity of certain OPs. Evidence for this was provided by cross-species comparisons, by administration of exogenous PON1 and by experiments in PON1 knockout and transgenic mice. Low PON1 plays also a role in the higher susceptibility of the young to OP toxicity. Recent findings also suggest that PON1 may modulate the toxicity resulting from exposure to mixtures of OP compounds

Keywords

Paraoxonase PON1 status organophosphate paraoxon chlorpyrifos oxon diazoxon