title: The carbonate radical anion-induced covalent aggregation of human copper, zinc superoxide dismutase, and alpha-synuclein: intermediacy of tryptophan- and tyrosine-derived oxidation products.
abstract: In this review, we describe the free radical mechanism of covalent aggregation of human copper, zinc superoxide dismutase (hSOD1). Bicarbonate anion (HCO3-) enhances the covalent aggregation of hSOD1 mediated by the SOD1 peroxidase-dependent formation of carbonate radical anion (CO3*-), a potent and selective oxidant. This species presumably diffuses out the active site of hSOD1 and reacts with tryptophan residue located on the surface of hSOD1. The oxidative degradation of tryptophan to kynurenine and N-formyl kynurenine results in the covalent crosslinking and aggregation of hSOD1. Implications of oxidant-mediated aggregation of hSOD1 in the increased cytotoxicity of motor neurons in amyotrophic lateral sclerosis are discussed.
authors.affiliation: Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226-0509, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Christopher
authors.initials: C
authors.lastname: Andrekopoulos
authors.forename: Joy
authors.initials: J
authors.lastname: Joseph
authors.forename: John
authors.initials: J
authors.lastname: Crow
authors.forename: B
authors.initials: B
authors.lastname: Kalyanaraman
mesh_terms: D002254:Carbonates / Q000737:chemistry*; D005609:Free Radicals; D006801:Humans; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000737:chemistry*; D051843:Synucleins; D014364:Tryptophan / Q000737:chemistry*; D051844:alpha-Synuclein
chemical_list: D002254:Carbonates; D005609:Free Radicals; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D014364:Tryptophan; D014442:Monophenol Monooxygenase; D013482:Superoxide Dismutase