The Role of Paraoxonase in Lipid Metabolism

Mackness, Michael I.; Durrington, Paul N.; Mackness, Bharti

doi:10.1007/978-1-4615-1027-7_4

Cited by 5 publications

(1 citation statement)

References 56 publications

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“…Early investigations centered around the role of the PON1 polymorphisms in resistance to organophosphorus insecticides (reviewed in Costa et al, ; La Du, ). More recent studies have focused on the role of the PON1 polymorphisms in vascular disease (reviewed in Lusis et al, ; Brophy et al, ; Mackness et al, ; Shih et al, ). These studies merit special comments.…”

Section: Commentarymentioning

confidence: 99%

Determination of Paraoxonase 1 Status and Genotypes at Specific Polymorphic Sites

et al. 2004

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The procedures for determining paraoxonase (PON1) status and for determining PON1 genotypes for polymorphisms in coding and important regulatory regions are described. PON1 status is determined by a functional two-substrate analysis of plasma PON1 activities. Differences in catalytic efficiency of the PON1₁₉₂Q and PON1₁₉₂R alloforms result in the clear separation of all three phenotypes at position 192 (Q/Q, Q/R, R/R) and at the same time, the two-substrate analysis indicates activity levels of PON1. Because the enzyme activity levels are as important as the polymorphic genotypes, this two-substrate analysis of PON1 status provides the most relevant information for investigating the association of PON1 genetics with susceptibilities to disease, organophosphorus insecticide sensitivity, and pharmacokinetic status of drug metabolism. Genotyping of polymorphic sites alone fails to provide this important information but can be useful for gene frequency determination and forensic analysis. Analytical procedures for determining PON1 status and genotypes are described.

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Section: Commentarymentioning

confidence: 99%

Determination of Paraoxonase 1 Status and Genotypes at Specific Polymorphic Sites

et al. 2004

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Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3

Teiber

Draganov

2003

Biochemical Pharmacology

150

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Polymorphisms of Paraoxonase (PON1) and Their Significance in Clinical Toxicology of Organophosphates

Costa

Cole

Furlong

2003

Journal of Toxicology: Clinical Toxicology

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Paraoxonase (PON1) is an HDL-associated enzyme capable of hydrolyzing multiple substrates, including several organophosphorous insecticides and nerve agents, oxidized lipids, and a number of drugs or pro-drugs. Several polymorphisms in the paraoxonase (PON1) gene have been described, which have been shown to affect either the catalytic efficiency of hydrolysis or the expression level of PON1. This review discusses the relevance of these polymorphisms for modulating sensitivity to organophosphorous compounds. Animal studies characterizing the PON1 polymorphisms have demonstrated the relevance of PON1 in modulating OP toxicity and have indicated the importance of an individual's PON1 status (i.e., genotype and phenotype taken together) rather than genotyping alone. Nevertheless, direct confirmation in humans of the relevance of PON1 status in conferring susceptibility to OP toxicity is still elusive. Recent studies examining the involvement of PON1 status in determining OP susceptibility of Gulf War veterans, sheep dippers, and individuals poisoned with chemical warfare agents represent a step in the right direction, but more studies are needed, with better documentation of both the level of exposure and the consequences of exposure.

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The Role of Paraoxonase in Lipid Metabolism

Cited by 5 publications

References 56 publications

Determination of Paraoxonase 1 Status and Genotypes at Specific Polymorphic Sites

Determination of Paraoxonase 1 Status and Genotypes at Specific Polymorphic Sites

Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3

Polymorphisms of Paraoxonase (PON1) and Their Significance in Clinical Toxicology of Organophosphates

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