Paraoxonase


Indications:

There is now good evidence that the antioxidant enzyme paraoxonase-1 (PON-1), which is associated with high density lipoprotein (HDL), exerts an anti-atherogenic effect by protecting low density lipoprotein (LDL) from oxidation.

HDL has a well-established inverse relationship with the risk of atherosclerosis [1,2]. HDL is required for the reverse transport of cholesterol from peripheral fibroblasts to the liver, but is also thought to protect LDL from oxidative modification, a key event in the initiation and acceleration of atherosclerosis [3,4]. The antioxidant role of HDL has been attributed to HDL-bound PON-1[5,6].

Paraoxonase (aryldialkylphosphatase EC 3.1.8.1, PON-1) is a calcium-dependant esterase that circulates in plasma associated bound to HDL [5,6]. It was originally identified by its activity in the metabolism of organophosphates [7,8] such as paraoxon, diazoxon, serin and soman, in addition to arylesters such as phenyl acetate [8]. It thus serves to neutralise anti-cholinesterase nerve gases and insecticides in the body [9]. PON-1 is synthesised in the liver and hence serum levels decrease in chronic liver disease [8].

Recent studies have confirmed that PON-1 is an oxidant-sensitive enzyme that inhibits the atherogenic oxidation of LDL [7]. Low PON-1 activity has been associated with a number of risk factors for coronary heart disease, including diabetes, hypercholesterolaemia and smoking [7]. It is well known, for example, that chronic renal failure results in accelerated atherosclerosis and studies have shown that haemodialysis increases production of reactive oxygen species while decreasing PON-1 activity [7,8]. There are also correlations between PON-1 enzyme levels and plasma lipids; PON-1 activity is lowered in familial hypercholesterolaemia, insulin dependent diabetes and amongst survivors of myocardial infarction [9].

PON-1 is an enzyme with three activities: paraoxonase, arylesterase and dyazoxonase [10]. Paraoxonase thus hydrolyses The paraoxonase and arylesterase activities of PON-1 both decrease in hypercholesterolaemia [10].

Pharmacologic therapy with simvastatin has been reported to increase serum PON-1 activity [6]. Pomegranate juice consumption or the intake of vitamin C and E supplements are also reported to raise enzyme levels [6].

Patient Instructions:

No special patient preparation is required prior to venipuncture.

Included in Profiles:

Included in Biolab Antioxidant Profile

Clinical Indications:

Serum paraoxonase (PON-1) is an antioxidant enzyme whose activity is associated with a decreased atherosclerosis risk; its measurement may therefore give useful information as to a subjectís cardiovascular risk. Since PON-1 is induced in oxidative stress, careful assessment of its serum activity is indicative of the subjectís ability to metabolise organophosphates and other xenobiotics.

Datasheet:

paraox.pdf (Click to Download)

Sample Requirements:

Green (lithium heparin)/Gold (SST) - Serum or plasma is suitable for paraoxonase measurement. The specimen of choice is whole blood, collected with heparin as an anticoagulant. However, the enzyme is calcium-dependent, so blood collected into other anti-coagulants such as EDTA is unsuitable for assay.

Postal Samples Acceptable:

Yes

References:

1. Miller GJ, Miller NE. Plasma high density lipoprotein concentration and the development of ischaemic heart disease. Lancet 1975;1:16-19.

2. Gordon DJ, Rifkind BM. High density lipoprotein the clinical implications of recent studies. N Engl J Med 1989;321:1311-1316.

3. Steinberg D, Parthasarathy S, Carew T et al. Beyond cholesterol; modifications of low density lipoprotein that increase atherogenecity. N Engl J Med 1998;320:933-937
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4. Mackness MI, Abbott CA, Arrol S et al. The role of high density lipoprotein and lipid soluble antioxidant vitamins in inhibiting low density lipoprotein oxidation. Biochem J 1993;294:829-834.

5. Mackness MI, Abbott CA, Arrol S et al. Protection of low density lipoprotein against oxidative modification by high density lipoprotein-associated paraoxonase. Atherosclerosis 1993;104:129-135.

6. Ferre N, Camps J, Fernandez-Ballart J et al. Regulation of serum paroxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem 2003;49(9):1491-1497

7. Sutherland WHF, de Jong S, Walker R. Hypochlorous acid and low serum paraoxonase activity in haemodyalsis patients; an in vitro study. Nephrol. Dial. Transplant 2004;19:75-82

8. Prakash M, Shetty JK, Rao L et al. Serum paraoxonase activity and protein thiols in chronic renal failure patients. Ind. J. Nephrol. 2008;18(1):13-16

9. Blatter Garin M, Abbott C, Messmer S et al. Quantification of human serum paraoxonase by enzyme-linked immunoassay: population differences in protein concentrations. Biochem. J. 1994;304:549-554

10. Nus M, Sanchez-Muniz J, Sanchez-Montero J. A new method for the determination of arylesterase activity in human serum using simulated body fluid. Atherosclerosis 2006;188:155-159

For further details please contact the laboratory at: lab@xxxxbiolab.co.uk