Covalent Modifications of Hemoglobin by Nitrite Anion: Formation Kinetics and Properties of Nitrihemoglobin

Department of Chemistry, Carnegie Mellon University, Mellon Institute, Pittsburgh, Pennsylvania 15213, USA.
Chemical Research in Toxicology (Impact Factor: 3.53). 10/2010; 23(11):1786-95. DOI: 10.1021/tx100242w
Source: PubMed


The green nitrihemoglobin (α(2)β(2) tetramer, NHb) was prepared by the aerobic reaction of excess nitrite with human hemoglobin A(0) under mildly acidic conditions. A rate equation was determined and found to depend on nitrite, hydrogen ion, and oxygen concentrations: -d[HbNO(2)]/dt = [k(1) + k(2)(K(a)[HNO(2)])[O(2)](1/2)][HbNO(2)], where k(1) = (2.4 ± 0.9) × 10(-4) s(-1), k(2) = (1 ± 0.2) × 10(5) M(-5/2) s(-1), and K(a) is the acid dissociation constant for nitrous acid (4.5 × 10(-4) M). Also, the chemical properties of NHb are compared to those of the normal hemoglobin (including the addition products of common oxidation states with exogenous ligands, the alkaline transitions of the ferric forms, and the oxygen binding characteristics of the ferrous forms) and were found to be nearly indistinguishable. Therefore, the replacement of a single vinyl hydrogen with a nitro group on the periphery of each macrocycle in hemoglobin does not significantly perturb the interaction between the hemes and the heme pockets. Because nonphotochemical reaction chemistry must necessarily be most dependent on electronic ground states, it follows that the clearly visible difference in color between hemoglobin A(0) and NHb must be associated primarily with the respective electronic excited states. The possibility of NHb formation in vivo and its likely consequences are considered.

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    • "Earlier studies were focusing on the methemoglobin-forming effect of nitrite that act as a scavenger by forming a relative stable complex of cyanomethemoglobin [3] [4]. Very recent studies are focusing on the mitochondria-linked mechanism of nitrite as a nitric oxide donor [9] [10] [11]. Extensive researches are also focusing on developing effective sulfur-containing compounds serving as sulfur donors for reacting with CN with or without Rh. "
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