The Ratio of Serum Paraoxonase/Arylesterase Activity Using an Improved Assay for Arylesterase Activity to Discriminate PON1R192 from PON1Q192

• Published in: Journal of Atherosclerosis and Thrombosis 2003, Vol.10(6), pp.337-342
• Main Authors: Nakanishi, Mamoru, Takanami, Yoshikazu, Maruyama, Taro, Murata, Mitsuru, Motohashi, Yoshiko, Nakano, Satomi, Uchida, Kagehiro, Maruyama, Chizuko, Kyotani, Shingo, Tsushima, Motoo
• Format: Article
• Language: English
• Subjects: Arylesterase; Atherosclerosis; Paraoxonase; Polymorphism
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.10.337

Human serum paraoxonase (PON1) exists in 2 major polymorphic forms: Q (glutamine) or R (arginine) at codon 192. The PON1192 activity polymorphism is substrate dependent. The PON1Q192 isoform has a higher rate of in vitro hydrolysis of diazoxon, sarin, and soman, whereas the PON1R192 isoform has higher activity for the hydrolysis of paraoxon and chlorpyrifos oxon. Both isoforms hydrolyze phenyl acetate at approximately the same rate. The present study described and evaluated a kinetic method of arylesterase activity determination with a modified fixed incubation method that used the oxidative coupling of phenol with 4-aminoantipyrine of phenyl acetate as the substrate. Our improved method shows that arylesterase activity is lower with the PON1R192 isoform than with the PON1Q192 isoform. The average activities of serum of individuals of a specific PON1Q192 genotype showed higher arylesterase and lower paraoxonase activity than the PON1R192 genotype. The ratio of paraoxonase/arylesterase activity showed a clear separation of all three PON1192 genotypes with no overlap between the groups (QQ: < 5.0, QR: 5.0−11.0, RR: > 11.0). PCR has suggested that the PON1192 phenotypes correspond to the PON1192 genotypes. Therefore, when conducting epidemiological or mechanistic studies that examine the role of PON1 in organophosphorus or lipid metabolism, this ratio is more useful and informative than a PCR-based genotype alone.