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HERO ID
1655048
Reference Type
Journal Article
Subtype
Review
Title
Characterization and function of mitochondrial nitric-oxide synthase
Author(s)
Giulivi, C
Year
2003
Is Peer Reviewed?
Yes
Journal
Free Radical Biology and Medicine
ISSN:
0891-5849
EISSN:
1873-4596
Volume
34
Issue
4
Page Numbers
397-408
Language
English
PMID
12566065
DOI
10.1016/S0891-5849(02)01298-4
Web of Science Id
WOS:000180733700001
Abstract
The mitochondrial production of nitric oxide is catalyzed by a nitric-oxide synthase. This enzyme has the same cofactor and substrate requirements as other constitutive nitric-oxide synthases. Its occurrence was demonstrated in various mitochondrial preparations (intact, purified mitochondria, permeabilized mitochondria, mitoplasts, submitochondrial particles) from different organs (liver, heart) and species (rat, pig). Endogenous nitric oxide reversibly inhibits oxygen consumption and ATP synthesis by competitive inhibition of cytochrome oxidase. The increased K(m) of cytochrome oxidase for oxygen and the steady-state reduction of the electron chain carriers provided experimental evidence for the direct interaction of this oxidase with endogenous nitric oxide. The increase in hydrogen peroxide production by nitric oxide-producing mitochondria not accompanied by the full reduction of the respiratory chain components indicated that cytochrome c oxidase utilizes nitric oxide as an alternative substrate. Finally, effectors or modulators of cytochrome oxidase (the irreversible step in oxidative phosphorylation) had been proposed during the last 40 years. Nitric oxide is the first molecule that fulfills this role (it is a competitive inhibitor, produced at a fair rate near the target site) extending the oxygen gradient to tissues.
Keywords
nitric oxide; mitochondria; free radicals; oxygen consumption; mitochondrial metabolism; nitric-oxide synthase
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