title: Melanogenesis inhibition by tetrahydropterines.
abstract: There is controversy in the literature concerning the action of tetrahydropterines on the enzyme tyrosinase and on melanogenesis in general. In this study, we demonstrate that tetrahydropterines can inhibit melanogenesis in several ways: i) by non-enzymatic inhibition involving purely chemical reactions reducing o-dopaquinone to L-dopa, ii) by acting as substrates which compete with L-tyr and L-dopa, since they are substrates of tyrosinase; and iii) by irreversibly inhibiting the enzymatic forms met-tyrosinase and deoxy-tyrosinase in anaerobic conditions. Three tetrahydropterines have been kinetically characterised as tyrosinase substrates: 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, 6-methyl-5,6,7,8-tetrahydropterine and 6,7-(R,S)-dimethyl-5,6,7,8-tetrahydropterine. A kinetic reaction mechanism is proposed to explain the oxidation of these compounds by tyrosinase.
authors.affiliation: GENZ: Grupo de Investigación de Enzimología, Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia, E-30100 Espinardo, Murcia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: García-Molina
authors.forename: J L
authors.initials: JL
authors.lastname: Munoz-Munoz
authors.forename: J R
authors.initials: JR
authors.lastname: Acosta
authors.forename: P A
authors.initials: PA
authors.lastname: García-Ruiz
authors.forename: J
authors.initials: J
authors.lastname: Tudela
authors.forename: F
authors.initials: F
authors.lastname: García-Cánovas
authors.forename: J N
authors.initials: JN
authors.lastname: Rodríguez-López
mesh_terms: D000363:Agaricales / Q000201:enzymology; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D011622:Pterins / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D011622:Pterins; C011552:tetrahydropterin; D014443:Tyrosine; D007980:Levodopa; D014442:Monophenol Monooxygenase