Paraoxonases are a group of enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s involved in the hydrolysis of organophosphate

Organophosphate

An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

s.

History

PON was identified as an enzyme having organophosphates as its substrate

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

s. Reports of the geographic differences in population frequencies of paraoxonase activity and genetic analysis

Genetic analysis

Genetic analysis can be used generally to describe methods both used in and resulting from the sciences of genetics and molecular biology, or to applications resulting from this research....

 led to uncovering the genetic polymorphism

Polymorphism (biology)

Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...

.

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
  PON1
  Paraoxonase 1 is a protein-coding gene. The protein encoded by this gene has esterase activity.-Function:PON1 is responsible for hydrolyising organophosphate pesticides and nerve gasses....
  
   is synthesized in the liver and transported along with HDL
  High density lipoprotein
  High-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
  
   in the plasma. It functions as an antioxidant
  Antioxidant
  An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
  
  ; it prevents the oxidation of LDL. Its serum concentration is influenced by inflammatory changes and the levels of serum oxidised-LDL.

• PON2
  PON2
  Serum paraoxonase/arylesterase 2 is an enzyme that in humans is encoded by the PON2 gene.-Further reading:...
  
   is a ubiquitously expressed intracellular protein that can protect cells against oxidative damage
  Oxidative stress
  Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
  
  .

• PON3
  PON3
  Paraoxonase 3, also known as PON3, is a protein which in humans is encoded by the PON3 gene.- Function :This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with...
  
   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

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

. PON1 and PON3 prevent the formation of atherogenic oxidised-LDL, the form of LDL present in foam cells of an atheromatous plaque.