Studies on human serum paraoxonase/arylesterase.
The complete amino acid sequence of human serum paraoxonase/arylesterase and the DNA sequence coding for that protein have recently been determined in two independent laboratories. There is now considerable evidence that the esterase exists in two genetically determined allozymic forms, and these A and B allozymes possess both paraoxonase and arylesterase activities. The B-type esterase has relatively higher paraoxonase activity and is stimulated to a greater degree by 1 M NaCl than the A allozyme. The structural basis for the distinctive isozymic properties is a single nucleotide base at position 572. Codon 191 is CAA (for glutamine) in the A-type esterase, and CGA (for arginine) in the B-type enzyme. There is a second polymorphic site which affects amino acid 54; this can be either methionine or leucine, but these alternatives 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 addition of phosphatidylcholine. The latter addition increases the maximum velocity rate, but does not alter the Km 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 importance of this association as far as the stability and catalytic properties of the esterase is not clear, and still under study. No physiological role of the esterase has been established, but its ability to hydrolyze several potent organophosphates may be of some significance in protecting against organophosphate toxicity.
Department of Pharmacology, Medical School, University of Michigan, Ann Arbor 48109-0572.
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D000595:Amino Acid Sequence; D043303:Aryldialkylphosphatase; D001483:Base Sequence; D002265:Carboxylic Ester Hydrolases / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D003062:Codon; D006801:Humans; D007527:Isoenzymes / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical
D003062:Codon; D007527:Isoenzymes; D010743:Phospholipids; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D010744:Phosphoric Monoester Hydrolases; D043303:Aryldialkylphosphatase