Paraoxonase

Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates.

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. 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.


 * 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.

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.