| Title | The functional nitrite reductase activity of the heme-globins. | | Author(s) | Gladwin MT, Kim-Shapiro DB | | Institution | Pulmonary and Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD, United States. | | Source | Blood 2008 Jul 2. | | Abstract | Hemoglobin and myoglobin are among the most extensively studied proteins in human history and nitrite one of the most studied small molecules. During the last decade, multiple physiological studies have surprisingly revealed that nitrite represents a biological reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. These studies suggest a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction in these processes. A biophysical and chemical analysis of the nitrite-deoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. The first is that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobin-nitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Thirdly, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of two molecules of nitrite into dinitrogen trioxide (N2O3), an uncharged molecule that can be exported from the erythrocyte. We will review these allosteric reactions of nitrite with the heme-globins in the context of historical studies of nitrite and hemoglobin chemistry, and attempt to place this novel functionality in the biological framework of hypoxic signaling in blood and the heart. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18596228 |
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