The human serum paraoxonase—Polymorphism and specificity

Abstract

Human serum contains EDTA‐sensitive (Ca++‐dependent) and EDTA‐stable (albumin) paraoxonases which hydrolyse paraoxon, 0,0‐diethyl,0–4‐nitrophenyl phosphate. In Caucasians the EDTA‐sensitive enzyme shows a genetically determined polymorphism which is governed by two alleles. In typical Mongoloid or Negro populations this polymorphism is expressed to a lesser degree, and in a few samples (e.g. Aborigines) it cannot be observed at all. The distribution of the activity of the EDTA‐stable (albumin) paraoxonase is unimodal. Many authors supposed that paraoxonase is an arylesterase (EC 3.1.1.2) which means that it is also able to hydrolyse phenylacetate or β‐naphthylacetate. New investigations have shown that the human serum fractions splitting paraoxon can be separated from those hydrolysing phenylacetate and related substrates. The polymorphism of the EDTA‐sensitive human serum paraoxonase can be applied to investigations concerning specificity. From this it becomes evident that this enzyme is rather specific. Already slight changes of the paraoxon molecule lead to a decrease of activity. On the other hand the enzyme seems to hydrolyse also phosphonic acid esters and 4‐nitrophenylacetate in the same way like paraoxon (polymorphism). There is a linkage relationship of paraoxonase with cystic fibrosis and DNA markers. According to these results the (EDTA‐sensitive) paraoxonase locus is on the human chromosome 7. A high serum paraoxonase level actually protects serum cholinesterase (EC 3.1.1.8) and has to be considered in biological monitoring of workers exposed to parathion.