Paraoxonase
| paraoxonase 1 | |
|---|---|
| Identifiers | |
| Symbol | PON1 |
| Alt. symbols | PON |
| Entrez | 5444 |
| HUGO | 9204 |
| OMIM | 168820 |
| RefSeq | NM_000446 |
| UniProt | P27169 |
| Other data | |
| EC number | 3.1.8.1 |
| Locus | Chr. 7 q21.3 |
| paraoxonase 2 | |
|---|---|
| Identifiers | |
| Symbol | PON2 |
| Entrez | 5445 |
| HUGO | 9205 |
| OMIM | 602447 |
| RefSeq | NM_000305 |
| UniProt | Q15165 |
| Other data | |
| EC number | 3.1.8.1 |
| Locus | Chr. 7 q21.3 |
| paraoxonase 3 | |
|---|---|
| Identifiers | |
| Symbol | PON3 |
| Entrez | 5446 |
| HUGO | 9206 |
| OMIM | 602720 |
| RefSeq | NM_000940 |
| UniProt | Q15166 |
| Other data | |
| EC number | 3.1.8.1 |
| Locus | Chr. 7 q21.3 |
Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates[1] and lactones.
History
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 in humans.[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. Serum PON3 activity is 100 times lower than PON1. 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.
3D structure
The 3D crytallographic structure of PON1 was determined in 2004.[6]
External links
References
- ↑ La Du BN (1992). "Human serum paraoxonase/arylesterase". In Kalow W, editor. Pharmacogenetics of drug metabolism. New York: Pergamon Press. pp. 51–91. ISBN 0-08-041175-4.
- ↑ Bergmeier C, Siekmeier R, Gross W (December 2004). "Distribution spectrum of paraoxonase activity in HDL fractions". Clin. Chem. 50 (12): 2309–15. doi:10.1373/clinchem.2004.034439. PMID 15459089.
- ↑ Li HL, Liu DP, Liang CC (2003). "Paraoxonase gene polymorphisms, oxidative stress, and diseases". JOURNAL OF MOLECULAR MEDICINE 81 (12): 766–779. doi:10.1007/s00109-003-0481-4. PMID 14551701.
- ↑ Ng CJ, Wadleigh DJ, Gangopadhyay A, et al. (November 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. PMID 11579088.
- ↑ Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM (April 2001). "Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids". Arterioscler. Thromb. Vasc. Biol. 21 (4): 542–7. doi:10.1161/01.ATV.21.4.542. PMID 11304470.
- ↑ PDB: 1V04; Proteopedia Paraoxonase; 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 (May 2004). "Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes". Nature Structural & Molecular Biology 11 (8): 412–9. doi:10.1038/nsmb767. PMID 15098021.
| ||||||||||||||||||