Paraoxonase 1 Status as a Risk Factor for Disease or Exposure

  • Rebecca J. Richter
  • Gail P. Jarvik
  • Clement E. Furlong
Conference paper

DOI: 10.1007/978-1-60761-350-3_4

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 660)
Cite this paper as:
Richter R.J., Jarvik G.P., Furlong C.E. (2010) Paraoxonase 1 Status as a Risk Factor for Disease or Exposure. In: Reddy S. (eds) Paraoxonases in Inflammation, Infection, and Toxicology. Advances in Experimental Medicine and Biology, vol 660. Humana Press

Abstract

Human paraoxonase 1 (PON1) has broad substrate specificity and has been shown to protect against exposure to some organophosphorus (OP) insecticides due to its ability to hydrolyze toxic metabolites of some organophosphorothioate insecticides. PON1 status has been shown to be important in protecting against vascular disease, presumably due to the not-as-yet fully characterized role of the three PON proteins in modulating oxidative stress. More recently, all three PONs (1, 2, and 3) have been shown to inactivate the quorum sensing factor N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) of Pseudomonas. Expression of human PON1 in Drosophila demonstrated the importance of PON1 in resistance to Pseudomonas infection. Many studies have examined only DNA single nucleotide polymorphisms as possible risk factors for disease or exposures. For all of the known functions of PON1, the level of PON1 enzyme is important and, in some cases, also the Q192R polymorphism. A simple high throughput two-substrate assay/analysis, plotting rates of diazoxon hydrolysis vs. paraoxon hydrolysis, provided both PON1 levels and functional Q192R phenotype/genotype. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates. Factors were determined for inter-converting rates of hydrolysis of different substrates.

Keywords

PON1 status Paraoxonase Diazoxon Diazinon Chlorpyrifos Chlorpyrifos oxon Carotid artery disease Quorum sensing factor OP exposure 

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rebecca J. Richter
    • 1
  • Gail P. Jarvik
    • 1
  • Clement E. Furlong
    • 1
  1. 1.Departments of Medicine (Division of Medical Genetics) and Genome SciencesUniversity of WashingtonSeattleUSA

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