The Human Serum paraoxonase/arylesterase Polymorphism

Am J Hum Genet. 1983 Nov;35(6):1126-38.

Abstract

The heterozygous human serum paraoxonase phenotype can be clearly distinguished from both homozygous phenotypes on the basis of its distinctive ratio of paraoxonase to arylesterase activities. A trimodal distribution of the ratio values was found with 348 individual serum samples, measuring the ratio of paraoxonase activity (with 1 M NaCl in the assay) to arylesterase activity, using phenylacetate. The three modes corresponded to the three paraoxonase phenotypes, A, AB, and B (individual genotypes), and the expected Mendelian segregation of the trait was observed within families. The paraoxonase/arylesterase activity ratio showed codominant inheritance. We have defined the genetic locus determining the aromatic esterase (arylesterase) responsible for the polymorphic paraoxonase activity as esterase-A (ESA) and have designated the two common alleles at this locus by the symbols ESA*A and ESA*B. The frequency of the ESA*A allele was estimated to be .685, and that of the ESA*B allele, 0.315, in a sample population of unrelated Caucasians from the United States. We postulate that a single serum enzyme, with both paraoxonase and arylesterase activity, exists in two different isozymic forms with qualitatively different properties, and that paraoxon is a "discriminating" substrate (having a polymorphic distribution of activity) and phenylacetate is a "nondiscriminating" substrate for the two isozymes. Biochemical evidence for this interpretation includes the cosegregation of the degree of stimulation of paraoxonase activity by salt and paraoxonase/arylesterase activity ratio characteristics; the very high correlation between both the basal (non-salt stimulated) and salt-stimulated paraoxonase activities with arylesterase activity; and the finding that phenylacetate is an inhibitor for paraoxonase activities in both A and B types of enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aryldialkylphosphatase
  • Female
  • Gene Frequency*
  • Genes*
  • Heterozygote
  • Homozygote
  • Humans
  • Isoenzymes / blood
  • Isoenzymes / genetics*
  • Male
  • Middle Aged
  • Paraoxon / analysis
  • Pedigree
  • Phenotype
  • Phenylacetates / analysis
  • Phosphoric Monoester Hydrolases / blood
  • Phosphoric Monoester Hydrolases / genetics*
  • Polymorphism, Genetic*
  • Substrate Specificity

Substances

  • Isoenzymes
  • Phenylacetates
  • Phosphoric Monoester Hydrolases
  • Aryldialkylphosphatase
  • Paraoxon