Iron stimulation of free radical-mediated porphyrinogen oxidation by hepatic and renal mitochondria.
Mitochondria from rat liver and kidney catalyze oxidation of uroporphyrinogen in the presence of NADH or succinate and the respiratory chain inhibitor, NaN3. The rate of porphyrinogen oxidation was substantially accelerated when iron as Fe+3-EDTA was added to reaction mixtures. This effect was partially attenuated by catalase, reduced glutathione (GSH) and other free radical scavengers. These results suggest that iron stimulates free radical-mediated porphyrinogen oxidation by tissue mitochondria under conditions of perturbed mitochondrial respiratory function. These observations suggest a mechanism by which iron could contribute to excess porphyrin excretion in various inherited or chemically-induced porphyrias.
Woods
J S
JS
Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Calas
C A
CA
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D010084:Oxidation-Reduction; D011165:Porphyrinogens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019810:Sodium Azide; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014577:Uroporphyrinogens / Q000378:metabolism*
D001386:Azides; D005290:Ferric Compounds; D005609:Free Radicals; D006878:Hydroxides; D011165:Porphyrinogens; D013386:Succinates; D014577:Uroporphyrinogens; D009243:NAD; D013481:Superoxides; D017665:Hydroxyl Radical; D019810:Sodium Azide; D004492:Edetic Acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; C019179:Fe(III)-EDTA