Peroxidase-promoted oxidation and peroxidation of the serotonergic neurotoxin 5,7-dihydroxytryptamine. A new pathway for its metabolic degradation.
Spectral data provide the first evidence that lactoperoxidase, a model enzyme for most mammalian peroxidases, catalyzed the one-electron oxidation and/or peroxidation of 5,7-dihydroxytryptamine. This process correlates with the production of superoxide radicals as is evident from the observed inhibitory effect of superoxide dismutase on product formation. 5,7-Dihydroxytryptamine is a classical peroxidase-oxidase substrate acting as a one-electron donor for enzyme compounds I, II and III. The one-electron peroxidatic oxidation of this serotonergic neurotoxin, responsible for the selective degeneration of central (5-hydroxytryptamine) neurons, is a fast process requiring measurement on the ms time scale. Attention is drawn to the biochemical and toxicological implications, because this fast reaction results in formation of known cell damaging species: free radicals, superoxide radicals and quinoidal products probably involved in the toxic action of 5,7-dihydroxytryptamine.
Metodiewa
D
D
Department of Chemistry, University of Alberta, Edmonton, Canada.
Dunford
H B
HB
D015116:5,7-Dihydroxytryptamine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007784:Lactoperoxidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D013053:Spectrophotometry
D015116:5,7-Dihydroxytryptamine; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase