The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysisof the toxic metabolites of a variety of organophosphorus insecticides. Theenzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenylacetate), and hence confer resistance to organophosphate toxicity []. Mammals have 3 distinct paraoxonase types, termed PON1-3 [, ]. In mice andhumans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum - the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity. Human and rabbit PONs appear to have two distinct Ca2+ binding sites, onerequired for stability and one required for catalytic activity. The Ca2+dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as theelectrophillic catalyst, like that proposed for phospholipase A2. Theparaoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of lowdensity lipoproteins (LPL) []. Although PON2 has oxidative properties, theenzyme does not associate with HDL.Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo [].
The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysisof the toxic metabolites of a variety of organophosphorus insecticides. Theenzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenylacetate), and hence confer resistance to organophosphate toxicity []. Mammals have 3 distinct paraoxonase types, termed PON1-3 [, ]. In mice andhumans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum - the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity. Human and rabbit PONs appear to have two distinct Ca2+ binding sites, onerequired for stability and one required for catalytic activity. The Ca2+dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as theelectrophillic catalyst, like that proposed for phospholipase A2. Theparaoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of lowdensity lipoproteins (LPL) []. Although PON2 has oxidative properties, theenzyme does not associate with HDL.Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo []. This family consists of arylesterases (Also known as serum paraoxonase) . These enzymes hydrolyse organophosphorus esters such as paraoxon and are found in the liver and blood. They confer resistance to organophosphate toxicity []. Human arylesterase (PON1) is associated with HDL and may protect against LDL oxidation [].
The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysisof the toxic metabolites of a variety of organophosphorus insecticides. Theenzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenylacetate), and hence confer resistance to organophosphate toxicity []. Mammals have 3 distinct paraoxonase types, termed PON1-3 [, ]. In mice andhumans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum - the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity. Human and rabbit PONs appear to have two distinct Ca2+ binding sites, onerequired for stability and one required for catalytic activity. The Ca2+dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as theelectrophillic catalyst, like that proposed for phospholipase A2. Theparaoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of lowdensity lipoproteins (LPL) []. Although PON2 has oxidative properties, theenzyme does not associate with HDL.Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo []. Rabbit and human serum PON1 also hydrolyse a variety oflactones and cycliccarbonate esters, including naturally occurring lactones and pharmacologicalagents []. Humans have 2 common PON1 allozymes, determined by the presenceof either arginine or glutamine at position 191. The A-type allozyme (glutamine at position 191) causes low paraoxonase activity []; thispolymorphism is associated with variations in cholesterol and lipoproteinlevels.
