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

Abstract

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. J Atheroscler Thromb, 2003; 10: 337-342.

Hyperhomocysteinemia, paraoxonase activity and risk of coronary artery disease

“…Nakanishi et al showed that arylesterase activity (with phenylacetate as substrate) is lower with the PON1 192RR than with PON1 192QQ genotypes in healthy Japanese subjects [31]. Q192R polymorphism has been widely studied, and the two alloenzymes have different affinities and catalytic activities towards a number of substrates [32].…”

Serum PON-1 Activity but not Q192R Polymorphism is Related to the Extent of Atherosclerosis

“…To date, multiple studies have examined the association between PON1 polymorphism and CAD 4, 13, [15][16][17][18][19][20][21][22][23][24][25][26] ; however, the vast ma- jority of studies neither concurrently assessed PON1 activity nor its relevance with the extent of angiographically documented atherosclerosis. In this study, we aimed at evaluating the relationship of PON1 (Q192R polymorphism and activity) with both CAD risk and the extent and severity of the disease.…”

“…R allozyme is less efficient at preventing the oxidation of LDL than the Q allozyme because of the decreased hydrolysis of lipid peroxides 13,14) . Hypothesized differences in the ability of the polymorphic forms to protect the oxidation of LDL have led to numerous studies attempting to determine the relationship between PON1 polymorphism and cardiovascular disease 4,13,[15][16][17][18][19][20][21][22][23][24][25][26] . These studies have yielded apparently conflicting results.…”

Serum paraoxonase 1 (PON1) activity and lipid metabolism parameters changes in different production cycle periods of Holstein-Friesian, Polish Red and Norwegian breeds

“…Human genotypes were characterized by P/A ratio respectively: QQ with P/A ratio below 5.0, QR within 5-11 and RR with P/A over 11 (Nakanishi et al 2003). Isoform PON1 R192 had higher paraoxonase activity than PON1 Q192.…”