Oxidation of Reduced Porphyrins by the Mitochondrial Electron Transport Chain: Stimulation by Iron and Potential Role of Reactive Oxygen Species

  • James S. Woods
  • Karen M. Sommer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Numerous studies have demonstrated a contributory role of iron in the pathogenesis of various inherited and chemically-induced disorders of porphyrin metabolism (porphyrias) (De Matteis et al, 1988, Smith and Francis, 1987, Lambrecht et al, 1988). However, the precise mechanism by which iron leads to excess tissue porphyrin accumulation and excretion in these disorders remains to be determined. Recent studies from these laboratories (Woods and Calas, 1989) have demonstrated that reduced porphyrins (porphyrinogens) are readily oxidized in vitro by reactive oxidizing species, such as superoxide (O 2 ) and hydroxyl (OH·) radicals, and that this effect is dramatically stimulated by the presence of iron compounds in the reaction mixture. Inasmuch as mitochondria are a principal locus both of porphyrin metabolism (e.g. Tait, 1978) as well as of the generation of reduced oxygen species (O 2 ), H2O2) (Forman and Boveris, 1982) in cells, it is reasonable to postulate that, in the presence of excess iron, reduced porphyrins could be oxidized by reactive oxidants derived from the mitochondrial electron transport chain, contributing to the accumulation and excretion of oxidized porphyrins observed in iron-exacerbated porphyrinopathies. The present studies were conducted to test the hypothesis that reduced porphyrins are oxidized by reactive oxidants derived from the mitochondrial electron transport chain in the presence of iron.


Xanthine Oxidase Mitochondrial Electron Transport Chain Minute Incubation Iron Lead Sample Cuvette 
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  1. Borg, D.C. and Schaich, K.M. (1987). Iron and iron-derived radicals, In: Oxygen Radicals and Tissue Injury. Proceedings of an Upjohn Symposium. ( Ed. Halliwell, B ), pp. 20–26.Google Scholar
  2. Boveris, A. and Chance, B. (1973). The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem. J. 134, 707–716.PubMedGoogle Scholar
  3. Bucher, J.R., Tein, M. and Aust, S.D. (1983). The requirement for ferric in the initiation of lipid peroxidation by chelated ferrous iron. Biochem. Biophys. Res. Commun. 111, 777–784.CrossRefPubMedGoogle Scholar
  4. Burkitt, M.J. and Gilbert, B.C. (1989). The control of iron-induced oxidative damage in isolated rat liver mitochondria by respiration state and ascorbate. Free Rad. Res. Commun. 5, 333–344.CrossRefGoogle Scholar
  5. De Matteis, F., Harvey, C., Reed, C. and Hempenius, R. (1988). Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Biochem. J. 250, 161–169.PubMedGoogle Scholar
  6. Forman, H.J. and Boveris, A. (1982). Superoxide radical and hydrogen peroxide in mitochondria. In: Free Radicals in Biology, Vol 5 (Ed. Pryor, WA ), pp. 65–90, Academic Press, New York.Google Scholar
  7. Halliwell, B. and Guttridge, J.M.C. (1984). Oxygen toxicity, oxygen radicals, transistion metals and disease. Biochem. J. 219, 1–4.PubMedGoogle Scholar
  8. Johnson, D. and Lardy, H. (1967). Isolation of liver and kidney mitochondria. Methods Enzymol. 10, 94–96.CrossRefGoogle Scholar
  9. Lambrecht, R.W., Sinclair, P.R., Bement, W.J., Sinclair, J.F., Carpenter, H.M., Buhler, D.R., Urquhart, A.J. and Elder, E.H. (1988). Hepatic uroporphyrin accumulation and uroporphyrinogen decarboxylase activity in cultured chick-embyyo hepatocytes and in Japanese quail and mice treated with polyhalogenated and aromatic compounds. Biochem. J. 253, 131–138.PubMedGoogle Scholar
  10. Loschen, G.L., Flohe, L. and Chance, B. (1971). Respiratory chain linked H202 production in pigeon heart mitochondria. FEBS. Lett. 18, 261–264.Google Scholar
  11. Smith A.G. and Francis, J.E. (1987). Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. Biochem. J. 246, 221–226.PubMedGoogle Scholar
  12. Smith, P.K., Krohn, R.I., Hermanson, G.T. (1985). Measurement of protein using bicinchoninic acid. Analytic. Biochem. 150, 76–85.CrossRefGoogle Scholar
  13. Tait, G.H. (1978). The biosynthesis and degradation of heme. In: Herne and Hemoproteins (Eds. De Matteis, F. and Aldridge, W.N. ), pp. 1–48, Springer-Verlag, Berlin.Google Scholar
  14. Woods, J.S. (1988). Attenuation of porphyrinogen oxidation by glutathione in vitro and reversal by porphyrinogenic trace metals. Biochem. Biophys. Res. Commun. 152, 1428–1434.CrossRefPubMedGoogle Scholar
  15. Woods, J.S. amd Calas, C.A. (1989). Iron stimulation of free radical-mediated porphyrinogen oxidation by hepatic and renal mitochondria. Biochem. Biophys. Res. Commun. 160, 101–08.CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • James S. Woods
    • 1
  • Karen M. Sommer
    • 1
  1. 1.Department of Environmental HealthUniversity of WashingtonSeattleUSA

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