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J. Biol. Chem., Vol. 277, Issue 16, 13556-13562, April 19, 2002
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From the Stimulation of cardiomyocytes to endogenously
evolve nitric oxide is shown by microsensor measurements on single
cells to lead to transient nitric oxide concentrations of a few hundred nanomolar. At these submicromolar concentrations, no evidence could be
found for the expected reaction between nitric oxide generated and the
oxymyoglobin present in the cells: nitric oxide + oxymyoglobin
The Catabolic Fate of Nitric Oxide
THE NITRIC OXIDE OXIDASE AND PEROXYNITRITE REDUCTASE ACTIVITIES
OF CYTOCHROME OXIDASE*
§,, and
§
Department of Environmental and Occupational
Health, University of Pittsburgh School of Public Health, Pittsburgh,
Pennsylvania 15261, ¶ Department of
Medicine/Renal Division, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania 15261, and
Department of Chemistry, Carnegie Mellon University,
Pittsburgh, Pennsylvania 15213 and Department of Pharmacology,
University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15261
nitrate + metmyoglobin. No metmyoglobin formation was detected by
electron paramagnetic resonance spectroscopy, and microsensor
measurements revealed near quantitative conversion of the nitric oxide
to nitrite rather than nitrate ion. Moreover, the rate of nitrite
formation is shown to be too rapid to be accounted for by non-enzymatic
means. The essentially quantitative and rapid catabolism of nitric
oxide to nitrite ion can plausibly be explained on the basis of a cycle
of reactions catalyzed by cytochrome c oxidase. It is
demonstrated with the purified hemoproteins in vitro that
the terminal oxidase can outcompete oxymyoglobin for available nitric
oxide. It is proposed that under normal physiological and most
pathological (non-inflammatory) conditions, reaction with cytochrome
c oxidase is the major route by which NO is removed from
mitochondria-rich cells.
*
This work was supported by Research Grants HL61411 (to
J. P. and B. R. P.) and HL57985 (to A. J. K.) from the NHLBI
National Institutes of Health and by Grant 9950029N from the American
Heart Association (to A. J. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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