Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

Figure 1

The heme oxygenase reaction. Heme oxygenase-1 catalyzes the rate-limiting step in heme degradation. The reaction produces biliverdin-IXα, carbon monoxide (CO), and ferrous iron (Fe II), at the expense of molecular oxygen and NADPH. Biliverdin-IXα produced in the HO reaction is then converted to bilirubin-IXα by biliverdin reductase. (Side chains are labeled as M: methyl, V: vinyl, P: propionate). The reactants and products of these enzymatic reactions have numerous and diverse biological sequelae. Heme is a vital molecule used in biosynthesis of cytochromes and other hemoproteins. Accumulation of this metabolite may promote deleterious oxidative reactions. Biliverdin-IXα and bilirubin-IXα may serve as cellular antioxidants, whereas circulating bilirubin may also provide antioxidant benefit in plasma. Bilirubin-IXα is conjugated by hepatic glucuronyltransferases and secreted by the biliary fecal route. CO has numerous signal transduction effects as outlined in this review. Systemic CO forms bind hemoglobin to form carboxyhemoglobin (CO-Hb). CO eventually diffuses to the lung where it is eliminated as exhaled CO (eCO). Fe (II) represents a potentially toxic metabolite of heme degradation. A potential metabolic fate of the released iron is sequestration by the iron storage protein ferritin.