PON1

PON1, or paraoxonase 1, is a calcium-dependent hydrolase encoded by the PON1 gene, part of the paraoxonase gene family located on chromosome 7. It is primarily synthesized in the liver and secreted into the plasma, where it associates with high-density lipoprotein (HDL).

In humans, PON1 exhibits several enzymatic activities, including paraoxonase (detoxification of organophosphates such as paraoxon), arylesterase, and lactonase. It contributes to the antioxidant function of HDL by hydrolyzing lipid peroxides and oxidized lipids, and may influence inflammation and cardiovascular risk.

Genetic variation affects activity. The two common coding-region SNPs are Q192R (rs662) and L55M (rs854560). In addition, a promoter polymorphism -108C>T influences expression levels. The 192R and 192Q alleles differ in substrate specificity; 192R generally hydrolyzes paraoxon more efficiently, while other substrates show different patterns. L55M affects serum PON1 concentrations and stability.

Clinical relevance: Lower PON1 activity has been linked with increased risk for cardiovascular disease and metabolic syndrome in some studies; lower detoxification capacity increases susceptibility to organophosphate poisoning. PON1 activity is influenced by age, sex, smoking, diet, and medications; and is usually determined by measuring catalytic activity with substrates such as paraoxon or phenyl acetate, alongside genotype.

PON1 is an HDL-associated enzyme, part of the body's defense against oxidative stress; research continues into its role in disease and toxic exposure, and its potential as a biomarker.