{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPON1 is a member of the paraoxonase gene family and is primarily a high‐density lipoprotein (HDL)–associated enzyme that displays lactonase activity. It hydrolyzes a broad spectrum of lactones—including oxidized fatty acid derivatives that likely represent its endogenous substrates—and is also present in plasma among several esterases. Its ability to bind HDL (particularly via apolipoprotein A‐I) markedly enhances both the enzyme’s catalytic efficiency and stability, which underpins its role in antioxidant defense and in maintaining lipid integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPON1 contributes to cardiovascular protection by preventing the oxidative modification of low‐density lipoproteins and other lipids—an action that is central to its antiatherogenic properties. Reduced PON1 activity or concentration has been associated with coronary heart disease, metabolic syndrome, and diabetic vascular complications, emphasizing its importance in lipid homeostasis and in counteracting systemic oxidative stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its antioxidative role, PON1 uniquely hydrolyzes organophosphates (for example, the detoxification of paraoxon) and is pivotal in converting prodrugs such as clopidogrel to their active metabolites—processes that are highly sensitive to common genetic polymorphisms (including the Q192R variant). These genetic differences, together with its inherent catalytic properties, influence not only the efficacy of drug bioactivation but also modulate susceptibility to toxic exposures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond lipid metabolism and detoxification, PON1 exhibits an even broader functional repertoire. It can hydrolyze bacterial quorum‐sensing molecules—thereby potentially modulating innate immune responses—and its genetic variability has been linked to differential outcomes in inflammatory and immune‐modulated conditions (for example, in anti–tumor necrosis factor therapy and diabetic retinopathy). Moreover, PON1 activity is subject to regulation by environmental and pharmacological factors (such as nutritional components and statins), and its polymorphisms have been implicated in conditions as diverse as neurodegenerative disorders and altered cholesterol biosynthesis. Interactions with other HDL–associated proteins, such as myeloperoxidase, further highlight the nuanced role of PON1 in vascular health and systemic inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dragomir I Draganov, John F Teiber, Audrey Speelman, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.str.0000016928.60995.bd"}], "href": "https://doi.org/10.1161/01.str.0000016928.60995.bd"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12052975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12052975"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Sarah Jane Mackenzie Ross, Chris Ray Brewin, Helen Valerie Curran, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI67478"}], "href": "https://doi.org/10.1172/JCI67478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23908111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23908111"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Chunyu Liu, Franak Batliwalla, Wentian Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A systematic meta-analysis of genetic association studies for diabetic retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db09-0059"}], "href": "https://doi.org/10.2337/db09-0059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19587357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19587357"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Egon A Ozer, Alejandro Pezzulo, Diana M Shih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEMS Microbiol Lett (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.femsle.2005.09.023"}], "href": "https://doi.org/10.1016/j.femsle.2005.09.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16260097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16260097"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ase Fredriksen, Klaus Meyer, Per Magne Ueland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20522"}], "href": "https://doi.org/10.1002/humu.20522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17436311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17436311"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "W H Wilson Tang, Jaana Hartiala, Yiying Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and genetic association of serum paraoxonase and arylesterase activities with cardiovascular risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.112.253930"}], "href": "https://doi.org/10.1161/ATVBAHA.112.253930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22982463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22982463"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sara Deakin, Ilia Leviev, Sophie Guernier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000096207.01487.36"}], "href": "https://doi.org/10.1161/01.ATV.0000096207.01487.36"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14500290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14500290"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Godfrey S Getz, Catherine A Reardon "}, {"type": "b", "children": [{"type": "t", "text": "Paraoxonase, a cardioprotective enzyme: continuing issues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Lipidol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00041433-200406000-00005"}], "href": "https://doi.org/10.1097/00041433-200406000-00005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15166781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15166781"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Martin D Tobin, Peter S Braund, Paul R Burton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotypes and haplotypes predisposing to myocardial infarction: a multilocus case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Heart J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ehj.2003.11.014"}], "href": "https://doi.org/10.1016/j.ehj.2003.11.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15039125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15039125"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Mariano Sentí, Marta Tomás, Montserrat Fitó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antioxidant paraoxonase 1 activity in the metabolic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2003-030648"}], "href": "https://doi.org/10.1210/jc.2003-030648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14602783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14602783"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Mike Mackness, Bharti Mackness "}, {"type": "b", "children": [{"type": "t", "text": "Paraoxonase 1 and atherosclerosis: is the gene or the protein more important?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2004.07.034"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2004.07.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15454272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15454272"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Elias Zintzaras, Georgios M Hadjigeorgiou "}, {"type": "b", "children": [{"type": "t", "text": "Association of paraoxonase 1 gene polymorphisms with risk of Parkinson's disease: a meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-004-0176-x"}], "href": "https://doi.org/10.1007/s10038-004-0176-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15368102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15368102"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "John F Teiber, Dragomir I Draganov, Bert N La Du "}, {"type": "b", "children": [{"type": "t", "text": "Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Pharmacol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-2952(03)00401-5"}], "href": "https://doi.org/10.1016/s0006-2952(03"}, {"type": "t", "text": "00401-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12963475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12963475"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "John F Teiber, Sven Horke, Donovan C Haines, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.01606-07"}], "href": "https://doi.org/10.1128/IAI.01606-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18347034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18347034"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Nicholas J Beaumont, Vernon O Skinner, Tricia M-M Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200575200"}], "href": "https://doi.org/10.1074/jbc.C200575200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12531885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12531885"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Dimitry A Chistiakov, Alexandra A Melnichenko, Alexander N Orekhov, et al. 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