title: 4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase.
abstract: 4-n-Butylresorcinol (BR) is considered the most potent inhibitor of tyrosinase, which is why it is used in cosmetics as a depigmenting agent. However, this work demonstrates that BR is a substrate of this enzyme. The Em (met-tyrosinase) form is not active on BR, but Eox (oxy-tyrosinase) can act on this molecule, hydroxylating it to o-diphenol. In turn, this is oxidized to an o-quinone, which isomerizes to a red p-quinone. Thus, for tyrosinase to act on this compound, a mechanism to generate Eox in the medium is required, which can be achieved by means of hydrogen peroxide or ascorbic acid. A kinetic analysis of the proposed mechanism allows its kinetic characterization: catalytic constant kcatBR (8.49 ± 0.20 s(-1) ) and Michaelis-constant KMBR (60.26 ± 8.76 μM). These findings are compared with those for other monophenolic substrates of tyrosinase. Studies of BR docking to the Em form of the enzyme show that the hydroxyl group in C-1 position is oriented toward the copper atom A (CuA), as in it is L-tyrosine. As regards Eox , BR is oriented with the carbon in C-6 position ready to be hydroxylated. The reaction of BR originates o-quinones, which isomerize to p-quinones, which in turn, could react with thiol compounds, a finding that could have important implications for pharmacology and the cosmetic industry. © 2016 IUBMB Life, 68(8):663-672, 2016.
authors.affiliation: Department of Biochemistry and Molecular Biology-A, GENZ-Group of Research on Enzymology (www.um.es/genz), Regional Campus of International Excellence "Campus Mare Nostrum,", University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Antonio
authors.identifier: 0000-0003-1099-5876
authors.initials: A
authors.lastname: Garcia-Jimenez
authors.affiliation: Department of Biochemistry and Molecular Biology-A, Group of Molecular Interactions in Membranes, University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Teruel-Puche
authors.affiliation: Department of Biochemistry and Molecular Biology-A, GENZ-Group of Research on Enzymology (www.um.es/genz), Regional Campus of International Excellence "Campus Mare Nostrum,", University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Carmen Vanessa
authors.initials: CV
authors.lastname: Ortiz-Ruiz
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Group of Synthetic Organic Chemistry, University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Berna
authors.affiliation: Department of Biochemistry and Molecular Biology-A, GENZ-Group of Research on Enzymology (www.um.es/genz), Regional Campus of International Excellence "Campus Mare Nostrum,", University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Tudela
authors.affiliation: Department of Biochemistry and Molecular Biology-A, GENZ-Group of Research on Enzymology (www.um.es/genz), Regional Campus of International Excellence "Campus Mare Nostrum,", University of Murcia, Espinardo, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Canovas
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003358:Cosmetics; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000737:chemistry* / Q000378:metabolism; D012118:Resorcinols / Q000737:chemistry* / Q000378:metabolism; D062327:Skin Lightening Preparations / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: C508220:4-n-butylresorcinol; D003358:Cosmetics; D012118:Resorcinols; D062327:Skin Lightening Preparations; D003300:Copper; D014442:Monophenol Monooxygenase
keywords: 4-n-butylresorcinol (BR); alternative substrate; inhibitor; kinetic analysis; tyrosinase