Serum paraoxonase (PON1) and its interactions with HDL: Relationship between PON1 and oxidative stress

Abstract

PON1 is a high density lipoprotein (HDL)-associated serum enzyme. Its primary function is to degrade commonly used insecticides and nerve gases. PON1 is found to be more effective than lecithin:cholesterol acyltransferase (LCAT) or apoA-I in protecting low density lipoproteins (LDL) against oxidation. This chapter reveals that the antioxidative properties of HDL can be compromised under conditions associated with accelerated atherosclerosis. It reveals that PON1 is largely responsible for the breakdown of lipid peroxides before they accumulate in LDL particles. In addition, PON1 also renders HDL resistant to oxidation and hydrolyzes lipid peroxides in human atherosclerotic lesions. The study also reveals that PON1 is primarily a lactonase acting upon certain lactones/hydroxyl acids. Therefore, one of the physiological roles of PON1 is the metabolism of lipid species arising from the oxidation of polyunsaturated fatty acids. The relationship between PON1 and HDL relies on a unique reciprocal arrangement. HDL facilitates the secretion of PON1 and offers a hydrophobic harbor for its anchoring. The chapter also provides a hydrophobic environment that is essential for optimal PON1 activity. In return, the enzyme prevents the oxidation of HDL and stimulates the cholesterol efflux from cells. Therefore, the association between PON1 and HDL is considered in both normal and pathological conditions.