Bicarbonate and active site zinc modulate the self-peroxidation of bovine copper-zinc superoxide dismutase.
Peroxidation reactions of copper-zinc superoxide dismutase (CuZn-SOD1) or its zinc-depleted form (CuE-SOD1) that likely also involve a component of bicarbonate buffer have been implicated in the pathophysiology of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), Alzheimer's Disease and Parkinson's Disease. Neither removal of the zinc ion nor adding bicarbonate had large effects on the self-peroxidation reaction of bovine SOD1, but the combination of zinc-deficiency and added bicarbonate caused major changes to the spin trapped SOD1-centred free radical. Removal of the active site zinc ion greatly decreased the formation of an unassigned SOD1-centred free radical in the reaction with the inorganic peroxide peroxynitrite. The results suggest that under cellular conditions ( approximately 5 mM bicarbonate) zinc-deficient SOD1 peroxidation could play a pathogenic role in neurodegenerative diseases.
Gunther
Michael R
MR
Department of Biochemistry and Molecular Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, USA. mgunther@hsc.wvu.edu
Donahue
Joseph A
JA
D000818:Animals; D001639:Bicarbonates / Q000737:chemistry*; D001665:Binding Sites; D002417:Cattle; D005609:Free Radicals / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry*; D019636:Neurodegenerative Diseases / Q000201:enzymology*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000737:chemistry; D011487:Protein Conformation; D013482:Superoxide Dismutase / Q000737:chemistry*; D000072105:Superoxide Dismutase-1; D015032:Zinc / Q000737:chemistry*
D001639:Bicarbonates; D005609:Free Radicals; D030421:Peroxynitrous Acid; D006639:Histidine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015032:Zinc