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 EDTAstable (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.

Oligomeric States of the Detergent-solubilized Human Serum Paraoxonase (PON1)

“…Evaluation of the Amount of Bound Detergent-HuPON1 was loaded on a 6-ml Q-Sepharose gel (see "Detergent Exchange") equilibrated in 0.36 mM C 12 E 8 in buffer A, washed by 60 ml of buffer A* (0.36 mM radiolabeled 14 C 12 E 8 at 0.031 Ci/ml in buffer A), and eluted by buffer B* (0.36 mM 14 C 12 E 8 at 0.031 Ci/ml in buffer A with NaCl 280 mM). 200 l of the more concentrated fraction (0.3 mg/ml) was loaded on a gel filtration column (Superose 12 HR 10 -30 from Amersham Biosciences) previously equilibrated in B* and eluted in the same buffer.…”

“…Fig. 7 shows the elution profiles of 200 and 100 l of HuPON1 injected at 0.3 and 1.2 mg/ml, respectively, in the presence of 0.36 mM radioactive 14 C 12 E 8 and the measurement of the radioactivity on the recovered fractions. From the measurement on three fractions on each of the two gel filtration columns eluted with radiolabeled C 12 E 8 , bound detergent ⌬ det was estimated to be 0.9 and 1.1 g of C 12 E 8 per g of HuPON1.…”

Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

“…Maternal urinary dialkyl phosphate metabolite levels in an agricultural population are correlated with shortened gestational length, a higher number of abnormal reflexes in neonates, and poorer neurodevelopment in young children (Eskenazi et al, 2004(Eskenazi et al, , 2007Young et al, 2005). Paraoxonase 1 (PON1) is an OP-hydrolyzing enzyme with high activity for detoxifying chlorpyrifos oxon (CPO) among many OPs (Geldmacher-von Mallinckrodt and Diepgen, 1988;Furlong et al, 1988). PON1 levels in children are often lowest at birth and can take up to 24 months or longer to reach adult levels (Augustinsson and Barr, 1963;Cole et al, 2003).…”

Pon1 Gene Polymorphism and Serum Paraoxonase Levels in Women Occupationally Exposed to Organophosphate Pesticides in South India.

“…It is hypothesized that individuals with low serum activity of this enzyme would be expected to have low ability to metabolize organophosphate compounds ( Geldmacher-von Mallinckrodt and Diepgen, 1988). Earlier studies on animals have also demonstrated the role of PON1 in decreasing the toxicity of organophosphate pesticides.…”