Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects

Abstract

Nitrite (NO₂⁻) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO₂⁻ and Hb(III)-NO₂⁻), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO₂⁻ to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O₂ supply to poorly oxygenated tissues, such as the eye's retina. Further, NO₂⁻ interacts with Mb(II)-O₂ and Hb(II)-O₂, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO₂⁻ through the O-nitrito binding mode (i.e., Fe-ONO⁻), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O⁻), like in most other heme-proteins. The structure-function relationships of the interaction of NO₂⁻ with both ferric and ferrous forms of Mb and Hb are discussed here.