Journal
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 38, Issue -, Pages 58-68Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2013.11.002
Keywords
Nitrite; Nitric oxide; Heme proteins; Xanthine oxidase; Aldehyde oxidase; Signal transduction
Categories
Funding
- NIH [HL058091, HL098032]
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It is now accepted that the anion nitrite, once considered an inert oxidation product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological blood pressure control, and redox signaling. As such, its application in therapeutics is being actively tested in pre-clinical models and in human phase I-II clinical trials. Major pathways for nitrite bioactivation involve its reduction to NO by members of the hemoglobin or molybdopterin family of proteins, or catalyzed dysproportionation. These conversions occur preferentially under hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. In this work, we review different proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics and experimental evidence for the relevance of each mechanism under different conditions. (c) 2013 Elsevier Inc. All rights reserved.
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