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PON1

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Template:PBB Serum paraoxonase/arylesterase 1 (PON1) also known as aromatic esterase 1 or serum aryldialkylphosphatase 1 is an enzyme that in humans is encoded by the PON1 gene.[1] Paraoxonase 1 has esterase and more specifically paraoxonase activity.[2]

Function

PON1 is responsible for hydrolysing organophosphate pesticides and nerve gasses. Polymorphisms in the PON1 gene significantly affect the catalytic ability of the enzyme.[3]

PON1 (paraoxonase 1) is also a major anti-atherosclerotic component of high-density lipoprotein (HDL).[4][5] The PON1 gene is activated by PPAR-γ, which increases synthesis and release of paraoxonase 1 enzyme from the liver, reducing atherosclerosis.[6] Its 3D structure was determined in 2004 and revealed that it is a six-bladed beta-propeller with a unique active site lid that is also involved in HDL binding[7][8]

[9]

Clinical significance

PON1 activity is low in infants compared to adults. A study of Mexican-American children showed that PON1 activity increased 3.5 times between birth and age seven.[10]

References

  1. ^ Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN (1996). "The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family". Genomics. 33 (3): 498–507. doi:10.1006/geno.1996.0225. PMID 8661009. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ van Himbergen TM, van Tits LJ, Roest M, Stalenhoef AF (2006). "The story of PON1: how an organophosphate-hydrolysing enzyme is becoming a player in cardiovascular medicine". Neth J Med. 64 (2): 34–8. PMID 16517986. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Costa LG, Cole TB, Vitalone A, Furlong CE (2005). "Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity". CLINICA CHEMICA ACTA. 352 (1–2): 37–47. doi:10.1016/j.cccn.2004.09.019. PMID 15653099.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Getz GS, Reardon CA (2005). "Paraoxonase, a cardioprotective enzyme: continuing issues". Curr. Opin. Lipidol. 15 (3): 261–7. doi:10.1097/00041433-200406000-00005. PMID 15166781.
  5. ^ Mackness M, Mackness B (2005). "Paraoxonase 1 and atherosclerosis: is the gene or the protein more important?". Free Radic. Biol. Med. 37 (9): 1317–23. doi:10.1016/j.freeradbiomed.2004.07.034. PMID 15454272.
  6. ^ Khateeb J, Gantman A, Kreitenberg AJ, Aviram M, Fuhrman B (2010). "Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway". Atherosclerosis. 208 (1): 119–25. doi:10.1016/j.atherosclerosis.2009.08.051. PMID 19783251. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ PMID: 15098021
  8. ^ PMID: 21217689
  9. ^ Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS (2004). "Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes". Nat Struct Mol Biol. 11 (5): 412–9. PMID 15098021.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Huen K, Harley K, Bradman A, Eskenazi B, Holland N (2010). "Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes". Toxicol. Appl. Pharmacol. 244 (2): 181–9. doi:10.1016/j.taap.2009.12.031. PMC 2846980. PMID 20045427. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

  • Furlong CE, Costa LG, Hassett C; et al. (1993). "Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification". Chem. Biol. Interact. 87 (1–3): 35–48. doi:10.1016/0009-2797(93)90023-R. PMID 8393745. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Furlong CE, Cole TB, Jarvik GP, Costa LG (2002). "Pharmacogenomic considerations of the paraoxonase polymorphisms". Pharmacogenomics. 3 (3): 341–8. doi:10.1517/14622416.3.3.341. PMID 12052142.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Mackness B, Durrington PN, Mackness MI (2003). "The paraoxonase gene family and coronary heart disease". Curr. Opin. Lipidol. 13 (4): 357–62. doi:10.1097/00041433-200208000-00002. PMID 12151850.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Costa LG, Cole TB, Furlong CE (2003). "Polymorphisms of paraoxonase (PON1) and their significance in clinical toxicology of organophosphates". J. Toxicol. Clin. Toxicol. 41 (1): 37–45. doi:10.1081/CLT-120018269. PMID 12645966.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Furlong CE, Cole TB, Jarvik GP; et al. (2005). "Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants". Neurotoxicology. 26 (4): 651–9. doi:10.1016/j.neuro.2004.08.002. PMID 16112327. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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