title: Mechanisms of nitrite bioactivation.
abstract: 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.
authors: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, United States; Translational Science Center, Wake Forest University, Winston-Salem, NC 27109, United States. Electronic address: shapiro@wfu.edu.
authors: Daniel B
authors: DB
authors: Kim-Shapiro
authors: Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: gladwinmt@upmc.edu.
authors: Mark T
authors: MT
authors: Gladwin
mesh_terms: D000818:Animals; D003067:Coenzymes / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008667:Metalloproteins / Q000378:metabolism; D000090006:Molybdenum Cofactors; D009573:Nitrites / Q000737:chemistry* / Q000378:metabolism*; D011621:Pteridines / Q000378:metabolism
chemical_list: D003067:Coenzymes; D006420:Hemeproteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D009573:Nitrites; D011621:Pteridines; C022261:molybdopterin
keywords: Aldehyde oxidase; Heme proteins; Nitric oxide; Nitrite; Signal transduction; Xanthine oxidase