کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2000641 | 1541621 | 2014 | 11 صفحه PDF | دانلود رایگان |
• Several mechanisms are fast enough to account for nitrite reduction in vivo.
• Different mechanisms are likely to predominate in different tissues and conditions.
• We suggest, deoxyhemoglobin plays a major role in nitrite-mediated vasodilation.
• Myoglobin, xanthine oxidase and aldehyde oxidase predominate in other tissues.
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.
Journal: Nitric Oxide - Volume 38, 30 April 2014, Pages 58–68