PON1 is responsible for hydrolysing organophosphate pesticides and nerve gasses. Polymorphisms in the PON1 gene significantly affect the catalytic ability of the enzyme. PON1 (paraoxonase 1) is also a major anti-atherosclerotic component of high-density lipoprotein (HDL). The PON1 gene is activated by PPAR-γ, which increases synthesis and release of paraoxonase 1 enzyme from the liver, reducing atherosclerosis. The "natural" substrates for PON1 appear to be lactones. However, PON1 has evolved to be a highly promiscuous enzyme capable of hydrolysing a wide variety of substrates such as lactones (including a number of important pharmaceutical agents such as statins), glucuronide drugs, thiolactones, arylesters, cyclic carbonates, organophosphorus pesticides and nerve gases such as sarin, soman and VX, oestrogen esters and lipid peroxides (oxidised lipids).