Paraoxon hydrolysis in human serum mediated by a genetically variable arylesterase and albumin.

Gel filtration chromatography resolves human serum paraoxonase into two fractions: (1) a high molecular weight fraction that is completely inhibited by EDTA and coelutes with arylesterase (E.C.3.1.1.2); and (2) a second 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 molecular weight 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. Our data suggest that albumin itself, rather than a protein bound to or cofractionating with albumin, mediates paraoxonase activity. The variation in levels of the activity of the nonalbumin, high molecular weight 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.