title: Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation.
abstract: When an antioxidant scavenges a reactive species, i.e., when it exerts its antioxidant activity, the antioxidant is converted into potentially harmful oxidation products. In this way, the antioxidant quercetin might yield an ortho-quinone, denoted as QQ, which has four tautomeric forms, i.e., the ortho-quinone and three quinonmethides. We evaluated the interaction of QQ with ascorbate or glutathione (GSH). Ascorbate recycles QQ to the parent compound quercetin, while GSH forms two adducts with QQ, i.e., 6-GSQ and 8-GSQ. When both GSH and ascorbate are present, QQ is converted exclusively into GSQ. In the absence of GSH, protein thiols will be arylated by QQ. This protein arylation is not prevented by ascorbate. Thiol arylation by quinones and quinonmethides can impair several vital enzymes. This implies that the product formed when quercetin displays its antioxidant scavenging effect is toxic in the absence of GSH. Therefore, an adequate GSH level should be maintained when quercetin is supplemented.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Maastricht University, The Netherlands. a.boots@farmaco.unimaas.nl
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Nard
authors.initials: N
authors.lastname: Kubben
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011794:Quercetin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000975:Antioxidants; D013438:Sulfhydryl Compounds; D011794:Quercetin; D006735:Horseradish Peroxidase; D005978:Glutathione; D001205:Ascorbic Acid