{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:55:04Z","timestamp":1768722904072,"version":"3.49.0"},"reference-count":73,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovenian Research Agency","award":["P1-0170"],"award-info":[{"award-number":["P1-0170"]}]},{"name":"Slovenian Research Agency","award":["J7-2600"],"award-info":[{"award-number":["J7-2600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cognitive impairment is a common non-motor symptom of Parkinson\u2019s disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia. In a cohort of PD patients, we compared a group of 89 patients with cognitive impairment with a group of 118 patients with normal cognition. We determined the kinetic parameters Km and Vmax for PON1 for the reaction with dihydrocoumarin and the genotype of four single nucleotide polymorphisms in PON1. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between PON1 rs662 and PON1 Km (p &lt; 10\u221210), between PON1 rs662 and PON1 Vmax (p = 9.33 \u00d7 10\u22127), and between PON1 rs705379 and PON1 Vmax (p = 2.21 \u00d7 10\u221210). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the PON1 genotype and enzyme kinetics in a large number of subjects. (2) It is the first study to report kinetic parameters of PON1 in a large number of subjects and to use time-concentration progress curves instead of initial velocities to determine Km and Vmax in a clinical context. (3) It is also the first study to calculate enzyme-kinetic parameters in a clinical context with a new algorithm for data point removal from progress curves, dubbed iFIT. Although our results suggest that in the context of PD, there is no clinically useful correlation between cognitive status on the one hand and PON1 genetic and enzyme-kinetic parameters on the other hand, this should not discourage future investigation into PON1\u2019s potential associations with other types of dementia.<\/jats:p>","DOI":"10.3390\/antiox12020399","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T02:28:17Z","timestamp":1675736897000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Bo\u0161tjan","family":"Petri\u010d","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Reden\u0161ek Trampu\u017e","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6707-6649","authenticated-orcid":false,"given":"Vita","family":"Dol\u017ean","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Gregori\u010d Kramberger","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center, 1000 Ljubljana, Slovenia"},{"name":"Chair of Neurology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Karolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, 141 83 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Tro\u0161t","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center, 1000 Ljubljana, Slovenia"},{"name":"Chair of Neurology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1709-6390","authenticated-orcid":false,"given":"Nikola","family":"Marakovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-7483","authenticated-orcid":false,"given":"Marko","family":"Goli\u010dnik","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7922-9745","authenticated-orcid":false,"given":"Aljo\u0161a","family":"Bavec","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jns.2009.08.034","article-title":"The epidemiology of dementia associated with Parkinson disease","volume":"289","author":"Aarsland","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sun, C., and Armstrong, M.J. (2021). Treatment of Parkinson\u2019s Disease with Cognitive Impairment: Current Approaches and Future Directions. Behav. Sci., 11.","DOI":"10.3390\/bs11040054"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/s41586-020-2388-4","article-title":"Reversing a model of Parkinson\u2019s disease with in situ converted nigral neurons","volume":"582","author":"Qian","year":"2020","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chang, K.-H., and Chen, C.-M. (2020). The Role of Oxidative Stress in Parkinson\u2019s Disease. Antioxidants, 9.","DOI":"10.3390\/antiox9070597"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1212\/01.wnl.0000183063.99107.5c","article-title":"Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease","volume":"65","author":"Irizarry","year":"2005","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jns.2004.05.007","article-title":"Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson\u2019s disease","volume":"223","author":"Sohmiya","year":"2004","journal-title":"J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.parkreldis.2007.06.009","article-title":"Plasma lipid peroxidation and antioxidant status of Parkinson\u2019s disease patients in the Indian population","volume":"14","author":"Sharma","year":"2008","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10072-016-2782-8","article-title":"Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson\u2019s disease","volume":"38","author":"Durak","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1515\/CCLM.2006.143","article-title":"Elevated plasma homocysteine levels in L-dopa-treated Parkinson\u2019s disease patients with dyskinesias","volume":"44","author":"Zoccolella","year":"2006","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3233\/JAD-2011-110587","article-title":"Serum and cerebrospinal fluid uric acid levels in lewy body disorders: Associations with disease occurrence and amyloid-\u03b2 pathway","volume":"27","author":"Maetzler","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s00415-012-6648-6","article-title":"Serum epidermal growth factor predicts cognitive functions in early, drug-naive Parkinson\u2019s disease patients","volume":"260","author":"Pellecchia","year":"2013","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/ana.22271","article-title":"Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease","volume":"69","author":"Hu","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bbi.2013.07.007","article-title":"Cerebrospinal fluid inflammatory markers in Parkinson\u2019s disease--associations with depression, fatigue, and cognitive impairment","volume":"33","author":"Lindqvist","year":"2013","journal-title":"Brain, Behav. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.1464-410X.2010.09888.x","article-title":"Paraoxonase-1 is only present in traceable amounts in seminal fluid and does not show any relationship with male subfertility","volume":"108","author":"Marsillach","year":"2011","journal-title":"BJU Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/rda.13015","article-title":"Paraoxonase 1 (PON1) activity in serum, follicular fluid and seminal plasma of sheep","volume":"52","author":"Rincon","year":"2017","journal-title":"Reprod. Domest. Anim."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.biocel.2016.06.008","article-title":"Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases","volume":"81","author":"Castellazzi","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eaaz9360","DOI":"10.1126\/sciadv.aaz9360","article-title":"Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer\u2019s disease","volume":"6","author":"Higginbotham","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Parkinsons Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.taap.2011.08.009","article-title":"Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases","volume":"256","author":"Androutsopoulos","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Harley, K.G., Huen, K., Aguilar Schall, R., Holland, N.T., Bradman, A., Barr, D.B., and Eskenazi, B. (2011). Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023923"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cbi.2010.03.033","article-title":"Human PON1, a biomarker of risk of disease and exposure","volume":"187","author":"Furlong","year":"2010","journal-title":"Chem. Interact."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ceron, J.J., Tecles, F., and Tvarijonaviciute, A. (2014). Serum paraoxonase 1 (PON1) measurement: An update. BMC Vet. Res., 10.","DOI":"10.1186\/1746-6148-10-74"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mota, A., Taheraghdam, A., and Valilo, M. (2019). Paraoxonase 1 and its relationship with Parkinson\u2019s disease. Brain Nerves, 4.","DOI":"10.15761\/JBN.1000120"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0006-8993(98)00586-1","article-title":"Genetic polymorphism of paraoxonase 1 (PON1) and susceptibility to Parkinson\u2019s disease","volume":"806","author":"Kondo","year":"1998","journal-title":"Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0022-510X(01)00439-7","article-title":"Paraoxonase 1 Met--Leu 54 polymorphism is associated with Parkinson\u2019s disease","volume":"184","author":"Akhmedova","year":"2001","journal-title":"J. Neurol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/mds.10172","article-title":"Further evidence for an association of the paraoxonase 1 (PON1) Met-54 allele with Parkinson\u2019s disease","volume":"17","author":"Carmine","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_27","first-page":"25","article-title":"Polimorfizmi gena citohrom oksidaze P450 2D6 (CYP2D6), paraoksonaze 1 (PON1) iapolipoproteina (APOE) kao faktori rizika od razvoja Parkinsonove bolesti = Polymorphisms in the genes of citohrom oxidase P450 2D6 (CYP2D6), paraxonase 1 (PON1) and apolipoprot","volume":"64","author":"Svetel","year":"2007","journal-title":"Mil. Med. Pharm. J. Serb."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/EDE.0b013e3181c15ec6","article-title":"Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease","volume":"21","author":"Manthripragada","year":"2010","journal-title":"Epidemiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.neulet.2004.05.108","article-title":"Paraoxonase 1 (PON1) gene polymorphisms and Parkinson\u2019s disease in a Finnish population","volume":"367","author":"Clarimon","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_30","first-page":"55","article-title":"Pesticides exposure and genetic polymorphism of paraoxonase in the susceptibility of Parkinson\u2019s disease","volume":"14","author":"Fong","year":"2005","journal-title":"Acta Neurol. Taiwan"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/oem.2006.032078","article-title":"Gene-environment interactions in parkinsonism and Parkinson\u2019s disease: The Geoparkinson study","volume":"64","author":"Dick","year":"2007","journal-title":"Occup. Environ. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"204.e13","DOI":"10.1016\/j.neurobiolaging.2010.08.010","article-title":"Paraoxonase-1 polymorphisms in Alzheimer\u2019s disease, Parkinson\u2019s disease, and AD-PD spectrum diseases","volume":"33","author":"Wingo","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.envint.2013.03.004","article-title":"Functional paraoxonase 1 variants modify the risk of Parkinson\u2019s disease due to organophosphate exposure","volume":"56","author":"Lee","year":"2013","journal-title":"Environ. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1089\/omi.2020.0160","article-title":"A Multi-Omics Analysis of PON1 Lactonase Activity in Relation to Human Health and Disease","volume":"25","author":"Kunej","year":"2021","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nsmb767","article-title":"Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes","volume":"11","author":"Harel","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tox.2018.10.012","article-title":"Paraoxonase-1 genetic polymorphisms in organophosphate metabolism","volume":"411","author":"Dardiotis","year":"2019","journal-title":"Toxicology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jocn.2013.04.025","article-title":"Paraoxonase and arylesterase activity and total oxidative\/anti-oxidative status in patients with idiopathic Parkinson\u2019s disease","volume":"21","author":"Kirbas","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000323265","article-title":"Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson\u2019s disease: Changes linked to disease progression","volume":"8","author":"Ikeda","year":"2011","journal-title":"Neurodegener. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135487","DOI":"10.1016\/j.neulet.2020.135487","article-title":"Association of -94 ATTG insertion\/deletion NFkB1 and c.*126G>A NFkBIA genetic polymorphisms with oxidative and nitrosative stress biomarkers in Brazilian subjects with Parkinson\u2019s Disease","volume":"740","author":"Baltus","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_40","first-page":"484","article-title":"Parkinson\u2019s Disease is Accompanied by Intertwined Alterations in Iron Metabolism and Activated Immune-inflammatory and Oxidative Stress Pathways","volume":"16","author":"Maes","year":"2017","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/jnc.13240","article-title":"Serum paraoxonase and arylesterase activities of paraoxonase-1 (PON-1), mild cognitive impairment, and 2-year conversion to dementia: A pilot study","volume":"135","author":"Cervellati","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"238","DOI":"10.23736\/S0026-4806.18.05875-5","article-title":"Evaluating the link between Paraoxonase-1 levels and Alzheimer\u2019s disease development","volume":"110","author":"Cervellati","year":"2019","journal-title":"Minerva Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Romani, A., Trentini, A., van der Flier, W.M., Bellini, T., Zuliani, G., Cervellati, C., and Teunissen, C.E. (2020). Arylesterase Activity of Paraoxonase-1 in Serum and Cerebrospinal Fluid of Patients with Alzheimer\u2019s Disease and Vascular Dementia. Antioxidants, 9.","DOI":"10.3390\/antiox9050456"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.17219\/acem\/111377","article-title":"Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia","volume":"29","author":"Berdowska","year":"2020","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tisato, V., Romani, A., Tavanti, E., Melloni, E., Milani, D., Bonaccorsi, G., Sanz, J.M., Gemmati, D., Passaro, A., and Cervellati, C. (2019). Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation. Antioxidants, 8.","DOI":"10.3390\/antiox8080287"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.redox.2018.01.001","article-title":"Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like K(m) instead of in vitro-like V(max)","volume":"15","author":"Veskoukis","year":"2018","journal-title":"Redox Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1172\/JCI67478","article-title":"Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex","volume":"123","author":"Huang","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"745438","DOI":"10.3389\/fnagi.2021.745438","article-title":"Experimental Models of Cognitive Impairment for Use in Parkinson\u2019s Disease Research: The Distance Between Reality and Ideal","volume":"13","author":"Fan","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fgene.2019.00461","article-title":"Clinical-Pharmacogenetic Predictive Models for Time to Occurrence of Levodopa Related Motor Complications in Parkinson\u2019s Disease","volume":"10","year":"2019","journal-title":"Front. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/10590501.2012.731957","article-title":"Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: A review","volume":"30","author":"Yuzhalin","year":"2012","journal-title":"J. Environ. Sci. Heal. Part C"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s12031-015-0620-8","article-title":"Association Between Paraoxonase Gene Polymorphisms and Intracerebral Hemorrhage in a Korean Population","volume":"57","author":"Park","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12958-020-00665-1","article-title":"Paraoxonase single nucleotide variants show associations with polycystic ovary syndrome: A meta-analysis","volume":"18","author":"Kunjantarachot","year":"2020","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1177\/1533317514539541","article-title":"Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer\u2019s disease and vascular dementia","volume":"29","author":"Alam","year":"2014","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dement."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1177\/0891988717731825","article-title":"A Meta-Analysis on the Relationship of the PON Genes and Alzheimer Disease","volume":"30","author":"Nie","year":"2017","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Petri\u010d, B., Goli\u010dnik, M., and Bavec, A. (2022). The Removal of Time-Concentration Data Points from Progress Curves Improves the Determination of K(m): The Example of Paraoxonase 1. Molecules, 27.","DOI":"10.3390\/molecules27041306"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1021\/ja01318a036","article-title":"The Determination of Enzyme Dissociation Constants","volume":"56","author":"Lineweaver","year":"1934","journal-title":"J. Am. Chem. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2478\/s11535-008-0035-4","article-title":"Uses and misuses of progress curve analysis in enzyme kinetics","volume":"3","author":"Nikolova","year":"2008","journal-title":"Open Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0167-4838(91)90007-M","article-title":"Experimental designs for estimating the parameters of the Michaelis-Menten equation from progress curves of enzyme-catalyzed reactions","volume":"1080","author":"Duggleby","year":"1991","journal-title":"Biochim. et Biophys. Acta (BBA)-Protein Struct. Mol. Enzym."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Bevc, S., Konc, J., Stojan, J., Hodo\u0161\u010dek, M., Penca, M., Praprotnik, M., and Jane\u017ei\u010d, D. (2011). {ENZO}: A Web Tool for Derivation and Evaluation of Kinetic Models of Enzyme Catalyzed Reactions. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022265"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1006\/abio.1996.0238","article-title":"Program DYNAFIT for the Analysis of Enzyme Kinetic Data: Application to HIV Proteinase","volume":"237","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/bmb.20479","article-title":"Exact and approximate solutions for the decades-old Michaelis-Menten equation: Progress-curve analysis through integrated rate equations","volume":"39","year":"2011","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1006\/jtbi.1997.0425","article-title":"Closed Form Solution for Time-dependent Enzyme Kinetics","volume":"187","author":"Schnell","year":"1997","journal-title":"J. Theor. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"478","DOI":"10.17344\/acsi.2022.7359","article-title":"iFIT: An automated web tool for determining enzyme-kinetic parameters based on the high-curvature region of progress curves","volume":"69","author":"Bavec","year":"2022","journal-title":"Acta Chim. Slov."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bse0590001","article-title":"Enzymes: Principles and biotechnological applications","volume":"59","author":"Robinson","year":"2015","journal-title":"Essays Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bej.2012.01.010","article-title":"On the Lambert W function and its utility in biochemical kinetics","volume":"63","year":"2012","journal-title":"Biochem. Eng. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bpc.2016.09.004","article-title":"On the estimation errors of KM and V from time-course experiments using the Michaelis\u2013Menten equation","volume":"219","author":"Stroberg","year":"2016","journal-title":"Biophys. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6371","DOI":"10.1021\/bi047440d","article-title":"Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase","volume":"44","author":"Khersonsky","year":"2005","journal-title":"Biochemistry"},{"key":"ref_69","first-page":"1335","article-title":"Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters","volume":"28","author":"Billecke","year":"2000","journal-title":"Drug Metab. Dispos."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1086\/320600","article-title":"Effects of 5\u2032 regulatory-region polymorphisms on paraoxonase-gene (PON1) expression","volume":"68","author":"Brophy","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0021-9150(99)00379-2","article-title":"A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression","volume":"150","author":"Suehiro","year":"2000","journal-title":"Atherosclerosis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1042\/bj20021670","article-title":"Paraoxonase-1 promoter haplotypes and serum paraoxonase: A predominant role for polymorphic position\u2014107, implicating the Sp1 transcription factor","volume":"372","author":"Deakin","year":"2003","journal-title":"Biochem. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1001\/jama.1993.03500180078038","article-title":"Population-Based Norms for the Mini-Mental State Examination by Age and Educational Level","volume":"269","author":"Crum","year":"1993","journal-title":"JAMA"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/399\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:26:14Z","timestamp":1760120774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["antiox12020399"],"URL":"https:\/\/doi.org\/10.3390\/antiox12020399","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}