The role of myeloperoxidase in the oxidation of biologically active polyhydroxyphenols (substituted catechols)

Abstract

The reaction of myeloperoxidase with biologically active polyhydroxyphenols (substituted catechols): catecholamine, norepinephrine and 2,4,5-trihydroxyphenylalanine [Phe(OH)3] were investigated by using the ESR spin-stabilization technique and rapid-scan spectrophometry in the millisecond time scale. The results presented here indicate that dihydroxyphenols and trihydroxyphenols are substrates in the myeloperoxidase reaction. The data of ESR and rapid-scan optical investigation of the myleoperoxidase reaction with the dihydroxyphenols catecholamine and norepinephrine clearly indicate a normal peroxidase-type pathway of catecholamine degradation. The first evidence of o-semiquinone radical formation as a product of the enzymatic oxidation of catecholamine by myeloperoxidase is reported. The results obtained by rapid-scan spectrophotometric investigation of enzyme intermediate formation and decay showed qualitative agreement with the spin-stabilization studies. The first results on the reaction of myeloperoxidase with the trihydroxyphenol Phe(OH)3 presented here, indicate that it plays a role as an electron donor for myeloperoxidase I, but we were unable to obtain evidence that a normal peroxidase cycle is occurring. The inhibitory effect of superoxide dismutase on product formation was evident and indicate the involvement of superoxide radicals in the process. Attention is drawn to the biochemical and toxicological implications of these and other related studies of substituted catechol peroxidation by mammalian peroxidases.