The paraoxonases: role in human diseases and methodological difficulties in measurement

Research into the paraoxonase (PON) gene family has flourished over the past few years. In the 1970s and 1980s, only PON1 was known, and the investigations were conducted, essentially, by toxicologists focusing on protection against organophosphate poisoning. Since then, two new members of the family, PON2 and PON3, have been identified, both being shown to play antioxidant and anti-inflammatory roles. Evidence exists indicating that the PON family is central to a wide variety of human illnesses such as cardiovascular disease, diabetes mellitus, metabolic syndrome, obesity, non-alcoholic steatohepatitis, and several mental disorders. However, research is hampered considerably by the methods currently available to measure the activity of these enzymes. In this review, we summarize the state of knowledge on PON biochemistry and function, the influence of genetic variations, and the involvement of PON in several diseases. The problems associated with PON measurement, such as sample acquisition, lack of reference methods, and variety of substrates, will be presented. Also, we cover some of the present lines of research and propose some others for future progress in this field.