STUDIES ON HUMAN SERUM PARAOXONASE ARYLESTERASE

The complete amino acid sequence of human serum paraoxonase/arylestera se and the DNA sequence coding for that protein have recently been det ermined in two independent laboratories. There is now considerable evi dence that the esterase exists in two genetically determined allozymic forms, and these A and B allozymes possess both paraoxonase and aryle sterase activities. The B-type esterase has relatively higher paraoxon ase activity and is, stimulated to a greater degree by 1 M NaCl than t he A allozyme. The structural basis for the distinctive isozymic prope rties is a single nucleotide base at position 572. Codon 191 is CAA (f or glutamine) in the A-type esterase, and CGA (for arginine) in the B- type enzyme. There is a second polymorphic site which affects amino ac id 54; this can be either methionine or leucine, but these alternative s have not been found to affect either the level or the quality of the allozymes. Purified A or B-type esterases are stimulated by the addit ion of phosphatidylcholine. The latter addition increases the maximum velocity rate, but does not alter the K(m) of the reaction with either paraoxon or phenylacetate. In serum, the esterase is tightly bound to the high density lipoproteins, particularly apo A-1, but the importan ce of this association as far as the stability and catalytic propertie s of the esterase is not clear, and still under study. No physiologica l role of the esterase has been established, but its ability to hydrol yze several potent organophosphates may be of some significance in pro tecting against organophosphate toxicity.