Paraoxonase-1 and its Interactions with HDL

Publisher Summary Paraoxonase-1 (PON1) is a plasma protein associated with high density lipoprotein (HDL) particles. PON1 is considered an enzyme with promiscuous functions and its physiological activity is likely to be lactonase. Furthermore, PON1 has an anti-atherogenic activity closely linked to its localization on HDL particles. PON1 is the most promising catalytic scavenger candidate for pretreatment and therapy of organophosphorus (OP) poisoning. Both the activity and stability of PON1 are highly dependent on the molecular environment of HDL components. A small subset of HDL particles with a complex dynamic structure is the major PON1 acceptor in plasma. Apolipoprotein J (apoJ), also known as clusterin, is a protein present in an HDL subpopulation together with PON1 and apoA-I. Its multiple functions include roles in complement regulation, lipid transport, apoptosis, and protection of membranes at fluid–tissue interfaces. Adiponectin, an adipose tissue secreted protein whose plasma concentration is positively correlated with HDL levels, was described as enhancing the hepatic production of PON1. HDL offers a hydrophobic harbor and a stabilizing environment for PON1 function(s). Akin to PON1 that displays multiple activities, HDL particles display long-lasting or transient binding capacity for numerous proteins involved in multiple biological mechanisms. HDL provides a vector that facilitates the enzyme secretion by offering a hydrophobic harbor for the retained signal peptide of PON1 and coincidentally stabilizing the enzyme.