The paraoxonase 1, 2 and 3 in humans [Humana paraoksonaza 1, 2 i 3]

Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Biochemia Medica (Impact Factor: 2.67). 06/2011; 21(2):122-30. DOI: 10.11613/BM.2011.020
Source: PubMed


The paraoxonase gene family in humans includes three members: PON1, PON2 and PON3. The products of those three genes are the following enzymes: paraoxonase 1 (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3). PON1 is mainly associated with a high density lipoprotein (HDL). A small amount of this enzyme is also bound to very low-density lipoprotein (VLDL) and postprandial chylomicrons. PON1 possess organophosphatase, arylesterase and lactonase activity and it hydrolyzes many different substrates. It is also known that PON1 may have antiatherogenic function. Compared to the PON1, PON2 and PON3 are much less studied and described. PON2 is ubiquitously expressed intracellular protein, while PON3 is bound to HDL, like PON1. The both enzymes possess antioxidant properties.

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    • "Obesity in MS may also induce changes in apoA1, due to high amounts of leptin, whose concentration increases gradually with fat mass. In turn, apoA1 is important, not only for PON1 transfer from hepatocytes to HDL, but also for PON1 activity [2] [5] [15] [25]. There are also changes in adipocyte secretion profile, which can turn them into real humoral factors secreting numerous biologically active peptides [15] [26]. "
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    ABSTRACT: The aim of the study was to investigate the influence of three single nucleotide polymorphisms (SNPs) (-108C>T, -162A>G and -909G>C) from the promoter region of paraoxonase 1 (PON1) gene on the enzyme activity, in patients with metabolic syndrome (MS). The study group consisted of 61 individuals with MS and the control group of 73 individuals without MS, matched for age and gender. For each individual, clinical and genetic parameters with possible influence on PON1 activities (paraoxonase, arylesterase and lactonase) were measured. PON1 genotyping was performed with PCR-RFLP, using specific primers and restriction enzymes. We found no differences for distribution of PON1 -108C>T, -162A>G and -909G>C polymorphisms, between the two groups (p-NS). The -108C>T and -909G>C polymorphisms were associated with paraoxonase (p=0.03, p=0.006, respectively), arylesterase (p<0.001, p<0.001, respectively) and lactonase (p<0.001, p<0.001, respectively) activities. The -162A>G polymorphism was not associated with paraoxonase (p-NS) or lactonase (p-NS) activities, but influenced the arylesterase activity (p=0.03). PON1 activities were influenced by all three polymorphisms, regardless of the presence of MS.
    Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 08/2015; 56(2):387-392. · 0.66 Impact Factor
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    ABSTRACT: Exposure to organophosphate (OP's) insecticides and nerve gases during the Persian Gulf War has been implicated in the development of Gulf War Syndrome. Paraoxonase (PON1) present in human serum detoxifies OP's. We determined the levels of PON1 in the serum of Gulf War Veterans and compared these to those found in a control population. One hundred fifty-two Gulf War Veterans from the UK who self-reported the presence of Gulf War Syndrome via a questionnaire and 152 age and gender matched controls were studied. PON1 activity, concentration, and genotype were determined. In the Gulf War Veterans, paraoxon hydrolysis was less than 50% of that found in the controls (100.3 (14.8-233.8) vs 214.6 (50.3-516.2) nmol/min/ml, P < 0.001). This low activity was independent of the effect of PON1 genotype. The serum PON1 concentration was also lower in the Gulf War Veterans (75.7 (18.1-351.3) vs 88.2 (34.5-527.4) microg/ml, P < 0.00025), which was again independent of PON1 genotype. There was no difference in the rate of diazoxon hydrolysis between the groups (10. 2 +/- 4.1 micromol/min/ml vs 9.86 +/- 4.4, P = NS). A decreased capacity to detoxify OP insecticides resulting from low serum PON1 activity may have contributed to the development of Gulf War Syndrome.
    Biochemical and Biophysical Research Communications 10/2000; 276(2):729-33. DOI:10.1006/bbrc.2000.3526 · 2.30 Impact Factor
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    ABSTRACT: Introduction: Paraoxonase-1 (PON1) is a Ca(2+) dependent, high-density lipoprotein-associated lactonase which is capable of retarding/inhibiting low-density lipoprotein (LDL) oxidation. LDL oxidation is believed to be central to the initiation and progression of atherosclerosis, therefore, PON1 is considered to be atheroprotective. Areas covered: Relevant literature on PON1 was identified in PubMed. Here, we discuss the background to research on PON1 in atherosclerosis, the evidence for and against PON1 being atheroprotective, potential mechanisms of this atheroprotection and current knowledge on human PON1 regulation. Expert opinion: Although current knowledge on PON1 indicates it to be atheroprotective, further clinical and basic studies are warranted to show that PON1 is causally linked to atherosclerosis, how it is atheroprotective and how it is regulated in vivo in humans.
    Expert Opinion on Therapeutic Targets 04/2013; 17(7). DOI:10.1517/14728222.2013.790367 · 5.14 Impact Factor
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