paraoxonase

Paraoxonase refers to a family of calcium-dependent hydrolases that includes three human enzymes: PON1, PON2, and PON3. These enzymes share structural similarity but differ in localization and substrate preferences. PON1 and PON3 are secreted and associate with high-density lipoprotein particles in plasma, whereas PON2 is primarily intracellular and broadly expressed.

PON1 exhibits paraoxonase and arylesterase activities and hydrolyzes organophosphate esters such as paraoxon and various lactones, contributing to detoxification and antioxidant protection against lipid peroxidation.

Genetic variation: PON1 activity is influenced by polymorphisms, notably Q192R and L55M (M/L notation varies by source), which change catalytic efficiency toward different substrates. Expression and activity are also modulated by lifestyle and health factors including diet, smoking, alcohol, age, and liver function.

PON2 provides cellular antioxidant defense and maintains hydrolytic activity on a distinct set of substrates, while PON3 circulates with HDL and shares lactonase activity with PON1. The trio collectively contributes to the body's handling of oxidative stress and xenobiotic compounds, though functional emphasis differs among the family members.

Clinical relevance: PON1 status influences detoxification of organophosphate pesticides and may modulate cardiovascular risk through HDL-associated antioxidant activity. Associations with pesticide sensitivity and cardiovascular disease have been reported, but findings are not uniformly concordant across populations.

Measurement and research: PON1 and related enzymes are assessed in the laboratory by examining paraoxonase or arylesterase activities and by genotyping common PON1 polymorphisms. Together these data help characterize enzyme capacity and inform epidemiological and toxicological studies.