Nitroxyl Accelerates the Oxidation of Oxyhemoglobin by Nitrite

Department of Physics, Wake Forest University, Winston-Salem, NC 27109.
Nitric Oxide (Impact Factor: 3.52). 03/2013; 31. DOI: 10.1016/j.niox.2013.03.006
Source: PubMed


Angeli’s salt (Na2N2O3) decomposes into nitroxyl (HNO) and nitrite , compounds of physiological and therapeutic interest for their impact on biological signaling both through nitric oxide and nitric oxide independent pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin. Earlier work has shown that HNO catalyzes the reduction of nitrite by deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the oxidation of oxygenated hemoglobin by . We have demonstrated this HNO mediated acceleration of the nitrite/oxygenated hemoglobin reaction with oxygenated hemoglobin being in excess to HNO and nitrite (as would be found under physiological conditions) by monitoring the formation of methemoglobin in the presence of Angeli’s salt with and without added . In addition, this acceleration has been demonstrated using the HNO donor 4-nitrosotetrahydro-2H-pyran-4-yl pivalate, a water-soluble acyloxy nitroso compound that does not release but generates HNO in the presence of esterase. This HNO donor was used both with and without and acceleration of the induced formation of methemoglobin was observed. We found that the acceleration was not substantially affected by catalase, superoxide dismutase, c-PTIO, or IHP, suggesting that it is not due to formation of extramolecular peroxide, NO2 or H2O2, or to modulation of allosteric properties. In addition, we found that the acceleration is not likely to be related to HNO binding to free reduced hemoglobin, as we found HNO binding to reduced hemoglobin to be much weaker than has previously been proposed. We suggest that the mechanism of the acceleration involves local propagation of autocatalysis in the nitrite-oxygenated Hb reaction. This acceleration of the nitrite oxyhemoglobin reaction could affect studies aimed at understanding physiological roles of HNO and perhaps nitrite and use of these agents in therapeutics such as hemolytic anemias, heart failure, and ischemia reperfusion injury.

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    ABSTRACT: Due to recent discoveries of important and novel biological activity, nitroxyl (HNO) has become a molecule of significant interest. Although it has been used in the past as a treatment for alcoholism, it is currently being touted as a treatment for heart failure. It is becoming increasingly clear that many of the biological actions of HNO can be attributed to its ability to react with specific thiol- and, possibly, heme-proteins. Herein is discussed the chemistry of HNO with likely biological targets. A particular focus is given to targets associated with the pharmacological utility of HNO as a cardiovascular agent and for the treatment of alcoholism.
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