Paraoxonase

protein
Name = paraoxonase 1
caption =


width =
HGNCid = 9204
Symbol = PON1
AltSymbols = PON
EntrezGene = 5444
OMIM = 168820
RefSeq = NM_000446
UniProt = P27169
PDB =
ECnumber = 3.1.8.1
Chromosome = 7
Arm = q
Band = 21.3
LocusSupplementaryData = protein
Name = paraoxonase 2
caption =


width =
HGNCid = 9205
Symbol = PON2
AltSymbols =
EntrezGene = 5445
OMIM = 602447
RefSeq = NM_000305
UniProt = Q15165
PDB =
ECnumber = 3.1.8.1
Chromosome = 7
Arm = q
Band = 21.3
LocusSupplementaryData = protein
Name = paraoxonase 3
caption =


width =
HGNCid = 9206
Symbol = PON3
AltSymbols =
EntrezGene = 5446
OMIM = 602720
RefSeq = NM_000940
UniProt = Q15166
PDB =
ECnumber = 3.1.8.1
Chromosome = 7
Arm = q
Band = 21.3
LocusSupplementaryData =

Paraoxonases are a group of enzymes invloved in the hydrolysis of organophosphates.cite book | author = La Du BN | authorlink = | editor = Kalow W, editor | others = | title = Pharmacogenetics of drug metabolism | edition = | language = | publisher = Pergamon Press | location = New York | year = 1992 | origyear = | pages = pages 51–91 | quote = | isbn = 0-08-041175-4 | oclc = | doi = | url = | accessdate = | chapter = Human serum paraoxonase/arylesterase ]

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. [cite journal |author=Bergmeier C, Siekmeier R, Gross W |title=Distribution spectrum of paraoxonase activity in HDL fractions |journal=Clin. Chem. |volume=50 |issue=12 |pages=2309–15 |year=2004 |month=December |pmid=15459089 |doi=10.1373/clinchem.2004.034439] 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. [cite journal |author=Ng CJ, Wadleigh DJ, Gangopadhyay A, "et al" |title=Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein |journal=J. Biol. Chem. |volume=276 |issue=48 |pages=44444–9 |year=2001 |month=November |pmid=11579088 |doi=10.1074/jbc.M105660200]

* 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.cite journal | author = Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM | title = Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 21 | issue = 4 | pages = 542–7 | year = 2001 | month = April | pmid = 11304470 | doi = | url = http://atvb.ahajournals.org/cgi/pmidlookup?view=long&pmid=11304470 | issn = ]

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.

External Links

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References