PARAOXON HYDROLYSIS IN HUMAN-SERUM MEDIATED BY A GENETICALLY VARIABLE ARYLESTERASE AND ALBUMIN

Abstract

Gel filtration chromatography resolves human serum paraoxonase into 2 fractions: a high MW fraction that is completely inhibited by EDTA and coelutes with arylesterase (EC 3.1.1.2); and a 2nd fraction that is closely associated with albumin, is only partially inhibited by EDTA, and has relatively little arylesterase activity under the assay conditions used. The activity of the high MW fraction is stimulated by NaCl, whereas the albumin associated activity is partially inhibited by NaCl and is not present in serum derived from an analbuminemic individual. Albumin itself, rather than a protein bound to or cofractionating with albumin, may mediate paraoxonase activity. The variation in levels of the activity of the nonalbumin, high MW enzyme is responsible for the observed polymorphism of paraoxonase activity in human serum or plasma. An optimal assay of polymorphic paraoxonase activity should be based on activity measurements of the nonalbumin fraction. It is considered likely that only the nonalbumin fraction is responsible for in vivo hydrolysis of paraoxon.