Metals and Paraoxonases

  • Lucio G. CostaEmail author
  • Toby B. Cole
  • Jacqueline M. Garrick
  • Judit Marsillach
  • Clement E. Furlong
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 18)


The paraoxonases (PONs) are a three-gene family which includes PON1, PON2, and PON3. PON1 and PON3 are synthesized primarily in the liver and a portion is secreted in the plasma, where they are associated with high-density lipoproteins (HDLs), while PON2 is an intracellular enzyme, expressed in most tissues and organs, including the brain. PON1 received its name from its ability to hydrolyze paraoxon, the active metabolite of the organophosphorus (OP) insecticide parathion, and also more efficiently hydrolyzes the active metabolites of several other OPs. PON2 and PON3 do not have OP-esterase activity, but all PONs are lactonases and are capable of hydrolyzing a variety of lactones, including certain drugs, endogenous compounds, and quorum-sensing signals of pathogenic bacteria. In addition, all PONs exert potent antioxidant effects. PONs play important roles in cardiovascular diseases and other oxidative stress-related diseases, modulate susceptibility to infection, and may provide neuroprotection (PON2). Hence, significant attention has been devoted to their modulation by a variety of dietary, pharmacological, lifestyle, or environmental factors. A number of metals have been shown in in vitro, animal, and human studies to mostly negatively modulate expression of PONs, particularly PON1, the most studied in this regard. In addition, different levels of expression of PONs may affect susceptibility to toxicity and neurotoxicity of metals due to their aforementioned antioxidant properties.


Paraoxonases Metals Lead Mercury Cadmium Manganese Oxidative stress 

























High-density lipoprotein








Low-density lipoprotein














Polymerase chain reaction




Parts per billion


Parts per million













Studies by the authors were supported in part by grants from NIEHS (P42ES004696, P30ES007033). We thank Dr. Wan-Fen Li and Ms. Rebecca Richter for their help with some of the experiments shown in Figs. 1, 2, and 3 and Dr. Renee LeBoeuf for providing the tissues of experiments shown in Fig. 4.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Lucio G. Costa
    • 1
    • 2
    Email author
  • Toby B. Cole
    • 1
    • 3
  • Jacqueline M. Garrick
    • 1
  • Judit Marsillach
    • 4
  • Clement E. Furlong
    • 4
    • 5
  1. 1.Department of Environmental and Occupational Health SciencesUniversity of WashingtonSeattleUSA
  2. 2.Department of Medicine & SurgeryUniversity of ParmaParmaItaly
  3. 3.Center on Human Development and DisabilityUniversity of WashingtonSeattleUSA
  4. 4.Department of Medicine (Division of Medical Genetics)University of WashingtonSeattleUSA
  5. 5.Department of Genome SciencesUniversity of WashingtonSeattleUSA

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