Characteristics of the genetically determined allozymic forms of human serum paraoxonase/arylesterase.
Human serum paraoxonase/arylesterase is an esterase with broad substrate specificity. It occurs in two genetically determined allozymic forms, which we have designated types A and B. These allozymes are presumed to be the products of two allelic genes located at the paraoxonase locus on chromosome 7, which is closely linked to the gene for cystic fibrosis. Paraoxonase activity of the B-type isozyme is considerably higher and stimulated more by 1 M NaCl than A-type paraoxonase. The ratio of paraoxonase activity/arylesterase activity of the B-isozyme is about 8, and that of the A-isozyme about 1. Purified isozymes A or B are free of nearly all other serum proteins, and the broad substrate specificity of the serum esterase is preserved after purification. A variety of substrates are hydrolyzed; these include: diisopropylfluorophosphate, soman, sarin, 4-nitro-phenylacetate, 2-nitro-phenylacetate, 2-naphthylacetate, and phenylthioacetate. The isozymic distinctions in kinetic properties and substrate specificity are preserved during purification. It is likely that the allozymes have very similar turnover numbers with phenylacetate (arylesterase activity), but differ considerably in their turnover numbers with paraoxon. Isozymes A and B have about the same minimal molecular weight of 43,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Further detailed studies on the individual isozymic proteins (or the DNA coding for their amino acid sequence) will be required to detect the exact structural differences in the isozymes.
Smolen
A
A
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Eckerson
H W
HW
Gan
K N
KN
Hailat
N
N
La Du
B N
BN
D002265:Carboxylic Ester Hydrolases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity
D007527:Isoenzymes; D011506:Proteins; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase