PON1 Active Protein

This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]

PON1: Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation. Genetic variation in PON1 is associated with susceptibility to microvascular complications of diabetes type 5 (MVCD5). These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new- onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Homozygosity for the Leu-54 allele is strongly associated with the development of retinal disease in diabetic patients. Belongs to the paraoxonase family.

Protein type: EC 3.1.8.1; EC 3.1.1.2; Lipid-binding; Secreted, signal peptide; Motility/polarity/chemotaxis; EC 3.1.1.81; Hydrolase; Phosphatase (non-protein); Secreted

Chromosomal Location of Human Ortholog: 7q21.3

Cellular Component: extracellular space; intracellular membrane-bound organelle; extracellular region

Molecular Function: protein homodimerization activity; arylesterase activity; phospholipid binding; calcium ion binding; aryldialkylphosphatase activity

Biological Process: response to external stimulus; response to nutrient levels; dephosphorylation; response to toxin; organophosphate catabolic process; positive regulation of transporter activity; carboxylic acid catabolic process; positive regulation of binding; aromatic compound catabolic process; phosphatidylcholine metabolic process

Disease: Microvascular Complications Of Diabetes, Susceptibility To, 5