The Oxidation of 3-Hydroxyanthranilic Acid by Cu,Zn Superoxide Dismutase: Mechanism and Possible Consequences

Authors: Liochev S.I.; Fridovich I.

Source: Archives of Biochemistry and Biophysics, Volume 388, Number 2, April 2001 , pp. 281-284(4)

Publisher: Academic Press

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Abstract:

Cu,Zn SOD, but not Mn SOD, catalyzes the oxidation of 3-hydroxyanthranilic acid (3-HA) under aerobic conditions. In the absence of O₂, the Cu(II) of the enzyme is reduced by 3-HA. One plausible mechanism involves the reduction of the active site Cu(II) to Cu(I), which is then reoxidized by the O^-₂ generated by autoxidation of the anthranilyl or other radicals on the pathway to cinnabarinate. We may call this the superoxide reductase, or SOR, mechanism. Another possibility invokes direct reoxidation of the active site Cu(I) by the anthranilyl, or other organic radicals, or by the peroxyl radicals generated by addition of O₂ to these organic radicals. Such oxidations catalyzed by Cu,Zn SOD could account for the deleterious effects of the mutant Cu,Zn SODs associated with familial amyotrophic lateral sclerosis and of the overproduction or overadministration of wild-type Cu,Zn SOD. Copyright 2001 Academic Press.

Keywords: 3-hydroxyanthranilic acid, oxidation of; Cu,Zn SOD, oxidation catalyzed by

Language: English

Document Type: Research article

Affiliations: The Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, 27710:

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