Peroxidase-promoted oxidation and peroxidation of the serotonergic neurotoxin 5,7-dihydroxytryptamine

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.Abbreviations 5-HT 5-Hydroxytryptamine, Serotonin - 5,7-DHT 5,7-Dihydroxytryptamine - 5,6-DHT 5,6-Dihydroxytryptamine - 5-HT-4,7-Dione 5-Hydroxytryptamine-4,7-Dione - GPO Glutathione Peroxidase - MAO Monoamine Oxidase - LPO Lactoperoxidase, the Roman numerals I, II and III added to LPO indicate compounds I, III and III of the enzyme - TPO Thyroid Peroxidase - IPO Intestinal Peroxidase - UPO Uterine Peroxidase - EPO Eosinophil Peroxidase - SOD Superoxide Dismutase - DPPH 1,1-Diphenyl-2-Picrylhydrazil radical - _max absorption maxima - ESR Electron Spin Resonance