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The carbonate radical anion-induced covalent aggregation of human copper, zinc superoxide dismutase, and alpha-synuclein: intermediacy of tryptophan- and tyrosine-derived oxidation products. Free Radic Biol Med 2004 Jun 01;36(11):1355-65

Date

05/12/2004

Pubmed ID

15135171

DOI

10.1016/j.freeradbiomed.2004.02.038

Scopus ID

2-s2.0-2342626577 (requires institutional sign-in at Scopus site)   63 Citations

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.

Author List

Zhang H, Andrekopoulos C, Joseph J, Crow J, Kalyanaraman B

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Carbonates
Free Radicals
Humans
Monophenol Monooxygenase
Nerve Tissue Proteins
Oxidation-Reduction
Superoxide Dismutase
Synucleins
Tryptophan
alpha-Synuclein