The human serum paraoxonase/arylesterase polymorphism.
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.
D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase; D005260:Female; D005787:Gene Frequency; D005796:Genes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010261:Paraoxon / Q000032:analysis; D010375:Pedigree; D010641:Phenotype; D010648:Phenylacetates / Q000032:analysis; D010744:Phosphoric Monoester Hydrolases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D013379:Substrate Specificity
D007527:Isoenzymes; D010648:Phenylacetates; D010744:Phosphoric Monoester Hydrolases; D043303:Aryldialkylphosphatase; D010261:Paraoxon