**2. Paraoxonase 1**

Oxidative stress due to reactive oxygen species results in oxidation of LDL particles and phospholipids, especially phosphatidylcholine, of the cell membrane of macrophages. This leads to a state of cellular damage and inflammation. It is possible that PON1 acts on oxidized phosphatidylcholine to produce lactone which further taken care by PON1 lactonase activity.

PON1 also exhibits homocysteine-thiolactonase activity. Homocysteine (Hcy) is a four-carbon amino acid with free thiol group formed by demethylation of methionine. Plasma Hcy levels are affected by both acquired and genetic factors [18, 19]. High levels of Hcy have been implicated in the development of cardiovascular and cerebrovascular disorders. Elevated Hcy has been shown to cause homocysteinylation, induction of oxidative stress and excitotoxicity, leading to atherosclerotic and thrombotic effects [20]. Hyperhomocysteinemia results in excess production of Homocysteine-thiolactone. This modifies proteins of coagulation, lipoproteins, endothelial receptors and is an important risk factor for adverse vascular events [21, 22]. Thus hyperhomocysteinemia, encompassing higher concentrations of homocysteine-thiolactone, may be an added risk factor for enhanced atherogenesis. PON1 has been postulated to detoxify the Hcy with its homocysteine-thiolactonase activity. At the same time, it can also protect macrophages from oxidation and prevents further inflammatory cascades. Hence the patients with low PON1 arylesterase and lactonase activity are more susceptible for the deleterious effects of lipid peroxidation, homocysteine-thiolactone toxicity and macrophage activation, which would increase the risk of neurovascular disease [23].

As a xenobiotic metabolizer, PON1 provides link between exposure to pesticides and adverse effects. The products formed by action of PON1 are considered to be the markers of pesticide exposure due to which they can be useful in the assessment of severity of pesticide exposure. Animal studies have demonstrated the potential application of PON1 in tackling the effect of pesticide poisoning. But more advanced and stringent clinical trials are required to support the definitive role in pesticide poisoning [5, 24]. PON1 response to pesticides depends upon the genetic polymorphism like Q192R, L55M. Literature reports that 192Q is more protective than 192R towards prevention of LDL oxidation.
