Abstract
Abstract Human serum paraoxonase 1 (PON1) appears to play an important role in the development of a large variety of diseases with an inflammatory component including heart disease, diabetes, rheumatic diseases, neurological diseases and cancer. As such PON1 research is rapidly expanding into new biomedical fields. Unfortunately, this rapid expansion has resulted in a number of problems due to poor experimental design and the spreading of misconceptions in the literature. This review seeks to describe the basic properties of PON1 and the problems and misconceptions that have arisen.
Highlights
The paraoxonase (PON) multi-gene family consists of three enzymes: paraoxonase 1 (PON1), PON2 and PON3
On the historical context of this controversy and how it was resolved [43, 44]. These basic facts about PON1 which were explained in this critical review have been known for over 20 years
The main misconceptions probably arise from authors either using old literature information (PON-1 is an esterase and PON-1 SNPs) or a lack of knowledge of PON-1 activity methods which use several different substrates to determine PON-1 activity
Summary
The paraoxonase (PON) multi-gene family consists of three enzymes: PON1, PON2 and PON3. PON1 is a highly promiscuous enzyme and will hydrolyse a large variety of substrates including lactones, thiolactones, organophosphorus triester pesticides and nerve gases (paraoxon, diazoxon, sarin and soman to name a few), arylesters, oestrogen-esters, cyclic carbamates and glucuronide drugs [1, 14] Due to these various enzymatic activities, the role of PON1 in detoxifying organophosphate compounds, drug metabolism, cardiovascular disease, and other diseases, has been extensively studied. PON3 has by far the highest activity towards two other eicosanoids, cycloepoxycyclopentenone (cyclo-EC) and 5,6 dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) followed by PON1 again with PON2 having little or no activity towards these substrates [22, 23] This order of hydrolytic efficacy applies to the hydrolysis of oestrogen esters by the PON family indicating a preference of PON3 for bulky cyclic groups. PON1 is subject to epigenetic regulation via DNA-methylation and microRNA binding, which, again has been the subject of extensive recent reviews [30,31,32] and not repeated here
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