Oxyhemoglobin, reaction with

The second reaction and certainly the major route for the destruction of nitric oxide in vivo is the fast and irreversible reaction with oxyhemoglobin (Hb) or oxymyoglobin to produce nitrate. 

Figure 11.3. Experimental findings that led to the identification of endothelium-derived relaxing factor (EDRF) as NO. The following observations were made with both EDRF and NO a Inactivation by oxyhemoglobin, associated with formation of methe-moglobin (top), and binding to hemoglobin, b Extended lifetime in the presence of superoxide dismutase. c Luminescence upon reaction with ozone.

Heme-containing proteins are also targets of -NO. Indeed, in vivo, quantitatively the major reaction of -NO is undoubtedly its reaction with oxyhemoglobin in the circulation to produce nitrate and methemoglobin... 

The increase in concentration of hydrogen ions inside the red blood cells promotes a reaction with oxyhemoglobin, which releases oxygen. 

Unfortunately, hemoglobin forms a complex with carbon monoxide that is considerably more stable than oxyhemoglobin. The equilibrium constant for the reaction... 

At the moment, only three in vitro studies have been performed on Bfx metabolic behavior, hi one case, it has been shown that Bfxs are able to be reduced by oxyhemoglobin to the corresponding o-nitroaniline derivatives (Scheme 5) [237]. hi the reaction between compoimd 135 and oxyhemoglobin compound 136 was generated as secondary product resulting from both nitrile hydrolysis and deoxygenation. This study indicates that blood is a possible site for metabolism of Bfxs with the consequent methemoglobinemia. 

Similar to peroxynitrite, ONOOCOO- reacts with many biomolecules such as uric acid [110], oxyhemoglobin [133], melatonin [135], NADH, ubiquinol Q0, and glutathione [141], Reactions of ONOOCOO with substrates in mitochondrial matrix is accompanied by protein nitration [141]. The reaction of ONOOCOO- with GSH was so rapid that glutathione inhibited tyrosine nitration by peroxynitrite in the presence of C02 [142], The formation of ONOOCOO- increased the formation of 3-nitrotyrosine and decreased the formation of 3-hydroxytyrosine probably due to the enhanced selectivity of C03 - compared to hydroxyl radicals [143],... 

The reactivity of NO with O2 is dramatically affected upon coordination of one of the diatomic components to a metal center. For example, the second-order reactions of NO with oxyhemoglobin, Hb(02) and oxymyoglobin, Mb(02) (e.g. Eq. (47)) are quite fast and have been used as colorimetric tests for NO (105). The nitrogen product is NO3 rather than N02 that is the product of aqueous autoxidation (106). While the reaction of 02 with nitrosyl myoglobin Mb(NO) (Eq. (48)) might superficially appear similar it is much slower and follows a different rate law (107). Possible mechanisms will be discussed below. 

In blood-containing vascular beds, the inactivation of nitric oxide by oxygen is of minor importance because of the rapid and irreversible reactions of nitric oxide with oxyhemoglobin in red blood cells. Any nitric oxide that diffuses into the vascular lumen will be quickly destroyed, making blood vessels effective sinks for nitric oxide. The half-life of nitric oxide is sufficiently long that nitric oxide diffusing into the vascular smooth muscle could also diffuse back out to the lumin to be inactivated by hemoglobin in red blood cells. 

Kosaka, H., Imaizumi, K., Imai, K., and Tyuma, 1. (1979). Stoichiometry of the reaction of oxyhemoglobin with nitrite. Biochim. Biophys. Acta 581, 184-188. 

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