Paraoxonase 1 (PON1) (PON1)

Paraoxonase 1 (PON1) is a multifaceted enzyme primarily synthesized in the liver and secreted into the bloodstream, where it associates with high-density lipoprotein (HDL) particles. It plays a pivotal role in the detoxification of organophosphate pesticides, a process often referred to as the "Biodegradation of diazinon," by catalyzing the hydrolytic cleavage of toxic metabolites like diazoxon. By rapidly neutralizing these potent inhibitors of acetylcholinesterase, PON1 serves as a critical biological defense mechanism against acute and chronic organophosphate poisoning. Beyond its role in xenobiotic metabolism, PON1 exhibits significant antioxidant properties, protecting low-density lipoproteins (LDL) from oxidative modification and thus acting as a protective factor against atherosclerosis and cardiovascular diseases. Genetic polymorphisms in the PON1 gene, such as the Q192R variant, significantly influence catalytic efficiency toward specific substrates, making it a key biomarker for individual susceptibility to chemical exposure. In drug discovery, PON1 is studied for its protective potential, with research exploring agents like statins and fibrates that can upregulate its expression to enhance metabolic and environmental resilience.

Other names

AryldialkylphosphataseA-esteraseSerum paraoxonase/arylesterase 1Organophosphate hydrolasePhosphotriesteraseDiazinon hydrolase

Enzymatic hydrolysis of organophosphorus esters and lactones; transcriptional and post-translational induction of enzyme activity by pharmacological agents.