PON1

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Paraoxonase 1
PDB 1v04 EBI.jpg
Rendering of 1V04
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PON1 ; ESA; MVCD5; PON
External IDs OMIM168820 MGI103295 HomoloGene68058 ChEMBL: 3167 GeneCards: PON1 Gene
EC number 3.1.1.2, 3.1.1.81, 3.1.8.1
RNA expression pattern
PBB GE PON1 206344 at tn.png
PBB GE PON1 206345 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5444 18979
Ensembl ENSG00000005421 ENSMUSG00000002588
UniProt P27169 P52430
RefSeq (mRNA) NM_000446 NM_011134
RefSeq (protein) NP_000437 NP_035264
Location (UCSC) Chr 7:
94.93 – 95.03 Mb
Chr 6:
5.17 – 5.19 Mb
PubMed search [1] [2]

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[edit]

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]

Structure[edit]

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]

Clinical significance[edit]

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.[8]

References[edit]

  1. ^ Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN (May 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. 
  2. ^ van Himbergen TM, van Tits LJ, Roest M, Stalenhoef AF (February 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. 
  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. 
  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 (January 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. 
  7. ^ 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. doi:10.1038/nsmb767. PMID 15098021. 
  8. ^ Huen K, Harley K, Bradman A, Eskenazi B, Holland N (April 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. 

Further reading[edit]

  • 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. 
  • 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. 
  • 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. 
  • 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. 
  • 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.