title: Physical and catalytic properties of a peroxidase derived from cytochrome c.
abstract: Except for its redox properties, cytochrome c is an inert protein. However, dissociation of the bond between methionine-80 and the heme iron converts the cytochrome into a peroxidase. Dissociation is accomplished by subjecting the cytochrome to various conditions, including proteolysis and hydrogen peroxide (H(2)O(2))-mediated oxidation. In affected cells of various neurological diseases, including Parkinson's disease, cytochrome c is released from the mitochondrial membrane and enters the cytosol. In the cytosol cytochrome c is exposed to cellular proteases and to H(2)O(2) produced by dysfunctional mitochondria and activated microglial cells. These could promote the formation of the peroxidase form of cytochrome c. In this study we investigated the catalytic and cytolytic properties of the peroxidase form of cytochrome c. These properties are qualitatively similar to those of other heme-containing peroxidases. Dopamine as well as sulfhydryl group-containing metabolites, including reduced glutathione and coenzyme A, are readily oxidized in the presence of H(2)O(2). This peroxidase also has cytolytic properties similar to myeloperoxidase, lactoperoxidase, and horseradish peroxidase. Cytolysis is inhibited by various reducing agents, including dopamine. Our data show that the peroxidase form of cytochrome c has catalytic and cytolytic properties that could account for at least some of the damage that leads to neuronal death in the parkinsonian brain.
authors.affiliation: Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. johannes.everse@ttuhsc.edu
authors.forename: Johannes
authors.initials: J
authors.lastname: Everse
authors.forename: Chyong-Jy J
authors.initials: CJ
authors.lastname: Liu
authors.forename: Penelope W
authors.initials: PW
authors.lastname: Coates
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine; D006801:Humans; D010300:Parkinson Disease; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D045304:Cytochromes c; D010544:Peroxidases; D004298:Dopamine