Hypoxemia and Attenuated Hypoxic Ventilatory Responses in Mice Lacking Heme Oxygenase-2

All nucleated cells depend on heme for their survival, as heme senses or uses oxygen. In fact, heme is a prosthetic moiety of various hemoproteins such as hemoglobin, myoglobin, and cytochromes. Accordingly, heme must be synthesized and degraded within an individual cell, because heme cannot be recycled among different cells, except for senescent erythrocytes, which are phagocytosed by macrophages in the reticuloendothelial system (for review, Shibahara, 2003). Heme, derived from hemoproteins, is broken down by heme oxygenase, which catalyzes the oxidative breakdown of heme, generating biliverdin, carbon monoxide (CO), and iron (Fig. 1). These heme degradation products are important bioactive molecules (For review, Shibahara, 2003 and references therein). Bilirubin functions as a chain-breaking antioxidant. CO represents a direct marker for heme catabolism, and binds to hemoglobin to form carboxyhemoglobin, which is transported to the lungs and is excreted in exhaled air. CO has received much attention because of its physiological functions similar to those of NO. Iron is transported to the entire tissues, especially bone marrow, and is reutilized for erythropoiesis and heme biosynthesis.