paraoxonase/arylesterase 1; serum aryldiakylphosphatase 1; A-esterase 1; aromatic esterase 1 (PON1 PON)

Function

• hydrolyzes paroxon
• hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides
• capable of hydrolyzing a broad spectrum of organophosphate substrates & a number of aromatic carboxylic acid esters
• may mediate enzymatic protection of low density lipoproteins against oxidative modification & the consequent series of events leading to atheroma formation
• heterooligomer with phosphate-binding protein (HPBP)
• association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo A1
• the retained signal peptide may allow transfer of the protein between phospholipid surfaces

a phenyl acetate + H2O <--> a phenol + acetate

an aryl dialkyl phosphate + H2O
              <-->
dialkyl phosphate + an aryl alcohol

Cofactor: Ca+2

• binds 2 Ca+2 per subunit

Structure

• glycosylated
• signal sequence is not cleaved
  • preferential association of PON1 with HDL is mediated, in part, by its signal peptide, by binding phospholipids directly, rather than binding apo AI
  • retained signal peptide may allow transfer of protein between phospholipid surfaces
• belongs to the paraoxonase family

Compartment

secreted, extracellular space

Expression

plasma, associated with HDL

Pathology

• PON1 gene mutations are associated with microvascular complications of diabetes mellitus

Polymorphism

• allozyme A, allelic form with Gln-192 hydrolyzes paraoxon with low turnover number &
• allozyme B, allelic form with Arg-192 hydrolyzes paraoxon with a high turnover number

Laboratory

• PON1 gene mutation
• PON1 in serum

More general terms

• paraoxonase, arylesterase or esterase-A
• Ca+2 binding protein

Database

• UniProt: http://www.uniprot.org/uniprot/P27169.html
• OMIM: https://mirror.omim.org/entry/168820