On the Biologic Role of the Reaction of NO with Oxidized Cytochrome c Oxidase
Abstract
The inhibition of cytochrome c oxidase (CcOX) by nitric oxide (NO) is analyzed with a mathematical model that simulates the metabolism in vivo. The main results were the following: (a) We derived novel equations for the catalysis of CcOX that can be used to predict CcOX inhibition in any tissue for any [NO] or [O(2)]; (b) Competitive inhibition (resulting from the reversible binding of NO to reduced CcOX) emerges has the sole relevant component of CcOX inhibition under state 3 in vivo; (c) In state 4, contribution of uncompetitive inhibition (resulting from the reaction of oxidized CcOX with NO) represents a significant nonmajority fraction of inhibition, being favored by high [O(2)]; and (d) The main biologic role of the reaction between NO and oxidized CcOX is to consume NO. By reducing [NO], this reaction stimulates, rather than inhibits, respiration. Finally, we propose that the biologic role of NO as an inhibitor of CcOX is twofold: in state 4, it avoids an excessive buildup of mitochondrial membrane potential that triggers rapid production of oxidants, and in state 3, increases the efficiency of oxidative phosphorylation by increasing the ADP/O ratio, supporting the therapeutic use of NO in situations in which mitochondria are dysfunctional.
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Modulation of mitochondrial respiration by CcOx is dependent on the state of oxidative phosphorylation.
“In addition, modulation of mitochondrial respiration by CcOx is dependent on the state of oxidative phosphorylation (55).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [55]
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Heart Mitochondrial Nitric Oxide Synthase
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Self-citation
- Authors
- Antunes, F., Boveris, A., & Cadenas, E.
- Affiliations
- University of Lisbon (PT)
- Universidad de Buenos Aires (AR)
- University of Southern California (US)
- ORCID
- Antunes, Fernando
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2007-10
- Volume
- 9
- Issue
- 10
- Pages
- 1569-1580
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1973707149
- Cited by
- 56
- References
- 56
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 14
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01 AG16718, R01AG016718)
- National Institute of Environmental Health Sciences (R01 ES 11342, R01ES011342)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, cytochrome c oxidase, competitive inhibition, uncompetitive inhibition, mitochondrial respiration, oxidative phosphorylation, ADP/O ratio, mitochondrial membrane potential, reactive oxygen species, mitochondrial dysfunction
- MeSH terms
- Catalysis, Electron Transport Complex IV, Nitric Oxide, Oxidation-Reduction, Ubiquinone
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