Reduction of manganese porphyrins by flavoenzymes and submitochondrial particles: a catalytic cycle for the reduction of peroxynitrite.

Published

Journal Article

The reduction of manganese(III) meso-tetrakis((N-ethyl)pyridinium-2-yl)porphyrin (MnTE-2-PyP) to manganese(II) was catalyzed by flavoenzymes such as xanthine oxidase and glucose oxidase, and by Complex I and Complex II of the mitochondrial electron transport chain. The reduced manganese porphyrin has been previously shown to react rapidly with superoxide and carbonate radical anion. Herein, we describe the reaction of a reduced manganese porphyrin with peroxynitrite that proceeds as a two-electron process, has a rate constant greater than 7 x 10(6) M(-1) s(-1) (at pH 7.25 and 37 degrees C), and produces nitrite and the Mn(IV)Porphyrin. The Mn(II)/Mn(IV) redox cycle was used to divert peroxynitrite from the inactivation of succinate dehydrogenase. In a typical experiment, 5 microM MnTE-2-PyP in the presence of excess succinate was able to protect the succinate dehydrogenase and succinate oxidase activities of submitochondrial particles challenged with a cumulative dose of 140 microM peroxynitrite infused in the course of 2 h. Other MnPorphyrins that are reduced more slowly do not provide as much protection underscoring the rate limiting character of the reduction step. The data presented here serve to rationalize the pharmacological action of MnPorphyrins as peroxynitrite reduction catalysts in vivo and opens avenues for the development of MnPorphyrins to protect mitochondria from oxidative damage.

Full Text

Duke Authors

Cited Authors

  • Ferrer-Sueta, G; Hannibal, L; Batinic-Haberle, I; Radi, R

Published Date

  • August 1, 2006

Published In

Volume / Issue

  • 41 / 3

Start / End Page

  • 503 - 512

PubMed ID

  • 16843831

Pubmed Central ID

  • 16843831

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2006.04.028

Language

  • eng

Conference Location

  • United States