Chapter 19 – Nitrite and Heme Globins: Reaction Mechanisms and Physiological Targets

Publisher Summary This chapter focuses on the mechanism and implications of hemoglobin-dependent nitrite reduction. It outlines the chemistry of this reaction, its subcellular targets, and the physiological implications of nitrite reduction. Nitrite is a dynamic endocrine storage form of NO and hemoglobin plays an integral role in reducing it to bioavailable NO. While the chemistry of hemoglobin- and myoglobin-dependent nitrite reduction is the same, the structural and redox properties of these two proteins determine their differing reaction kinetics. In addition, the physiological targets of these reactions differ due to their localization in different biological compartments. While hemoglobin-mediated nitrite reduction is responsible for hypoxic vasodilation, mitochondria are a major target for myoglobin-dependent nitrite reduction. Nitrite is an important mediator of many physiological responses. The family of hemoglobin proteins – including hemoglobin, neuroglobin, and myoglobin – play a central role in the bioactivation of nitrite by reacting with the molecule to reduce it to bioavailable NO under physiological and pathological hypoxic conditions. Hemoglobin- and myoglobin-dependent nitrite reduction to NO has been hypothesized to contribute to fundamental physiological responses, including hypoxic vasodilation and the regulation of hypoxic mitochondrial function. Future studies will determine whether neuroglobin and cytoglobin act as functional nitrite reductases in vivo and whether the nitrite reductase activity of all these globins can be harnessed for therapeutic applications.