Biological Implications of Heme Metabolism

Free heme, i.e., protein-unbound heme, can be toxic to cells because it catalyzes the production of reactive oxygen species. To cope with this problem, the body is equipped with various defense mechanisms against high free heme concentrations. Heme oxygenase is the key molecule in the elimination of the prooxidant heme, which catalyzes the conversion of free heme to iron, biliverdin IXα and carbon monoxide. Heme oxygenase-1 is a signature of oxidative tissue injury and plays a critical role in the defense against oxidative stress, while heme oxygenase-2 is now also recognized as an oxygen sensor. Both biliverdin IXα and carbon monoxide have been shown to be important in the protective response against oxidative tissue injuries. Thus, the breakdown products of heme have their own biological functions. Recent evidence suggests that there may be oscillatory control of both heme synthesis and oxidative stress. These findings suggest that heme metabolites may also be important in tissue protection, oxygen sensing, and circadian control of oxidative tissue injury.