title: Catalytic oxidation of acetaminophen by tyrosinase in the presence of L-proline: a kinetic study.
abstract: A kinetic study of acetaminophen oxidation by tyrosinase in the presence of a physiological nucleophilic agent such as the amino acid L-proline is performed in the present paper. The o-quinone product of the catalytic activity, 4-acetamido-o-benzoquinone, becomes unstable through the chemical addition of L-proline, in competition with the nucleophilic addition of hydroxide ion from water. In both cases, the catechol intermediate, 3(')-hydroxyacetaminophen, is generated, as can be demonstrated by liquid chromatography. When the effect of the presence of the nucleophilic agent on the time course of the enzymatic reaction was kinetically analyzed, it was seen to decrease the duration of the lag period and increase the steady-state rate. Rate constants for the reaction of 4-acetamido-o-benzoquinone with water and L-proline were also determined. The results obtained in this paper open a new possibility to acetaminophen toxicity, that has been attributed hitherto to its corresponding p-quinone, N-acetyl-p-benzoquinone imine.
authors.affiliation: GMB: Grupo de Modelización en Bioquímica, Departamento de Química-Física, Escuela Politécnica Superior de Albacete, Universidad de Castilla-La Mancha, Campus Universitario, Albacete E-02071, Spain. Edelmira.Valero@uclm.es
authors.forename: Edelmira
authors.initials: E
authors.lastname: Valero
authors.forename: Ramón
authors.initials: R
authors.lastname: Varón
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Carmona
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000737:chemistry*; D016227:Benzoquinones / Q000138:chemical synthesis*; D002384:Catalysis; D004789:Enzyme Activation; D007700:Kinetics; D008956:Models, Chemical; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D010084:Oxidation-Reduction; D011392:Proline / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
chemical_list: D016227:Benzoquinones; D012996:Solutions; D000082:Acetaminophen; C046225:2-acetamido-4-benzoquinone; D011392:Proline; D014442:Monophenol Monooxygenase; C027361:3-hydroxyacetaminophen