Catalytic oxidation of acetaminophen by tyrosinase in the presence of L-proline: a kinetic study.
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.
Valero
Edelmira
E
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
Varón
Ramón
R
García-Carmona
Francisco
F
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
D016227:Benzoquinones; D012996:Solutions; D000082:Acetaminophen; C046225:2-acetamido-4-benzoquinone; D011392:Proline; D014442:Monophenol Monooxygenase; C027361:3-hydroxyacetaminophen