PON was identified as an enzyme having organophosphates as its substrates. Reports of the geographic differences in population frequencies of paraoxonase activity and genetic analysis led to uncovering the genetic polymorphism.
Types
There are 3 known genotypic forms of paraoxonases. They are coded for by the PON set of genes – PON1, PON2 and PON3 – located on the long arm of chromosome 7.[2][3] The differences between them lie in their location and activity.
PON1 is synthesized in the liver and transported along with HDL in the plasma. It functions as an antioxidant; it prevents the oxidation of LDL. Its serum concentration is influenced by inflammatory changes and the levels of serum oxidised-LDL.
PON2 is a ubiquitously expressed intracellular protein that can protect cells against oxidative damage.[4]
PON3 is similar to PON1 in activity but differs from it in substrate specificity. Additionally, it is not regulated by inflammation and levels of oxidised lipids.[5]
Clinical Significance
PON1 and PON3 are implicated in lowering the risk of developing coronary artery disease and atherosclerosis. PON1 and PON3 prevent the formation of atherogenic oxidised-LDL, the form of LDL present in foam cells of an atheromatous plaque.
^La Du BN (1992). "Human serum paraoxonase/arylesterase". In Kalow W, editor (ed.). Pharmacogenetics of drug metabolism. New York: Pergamon Press. pp. pages 51–91. ISBN0-08-041175-4. {{cite book}}: |editor= has generic name (help); |pages= has extra text (help)
^Bergmeier C, Siekmeier R, Gross W (2004). "Distribution spectrum of paraoxonase activity in HDL fractions". Clin. Chem. 50 (12): 2309–15. doi:10.1373/clinchem.2004.034439. PMID15459089. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^Li HL, Liu DP, Liang CC (2003). "Paraoxonase gene polymorphisms, oxidative stress, and diseases". JOURNAL OF MOLECULAR MEDICINE. 81 (12): 766–779. PMID14551701.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Ng CJ; Wadleigh DJ; Gangopadhyay A; et al. (2001). "Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein". J. Biol. Chem. 276 (48): 44444–9. doi:10.1074/jbc.M105660200. PMID11579088. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
