32] Release of iron from hemoglobin

Abstract

This chapter discusses the release of iron from hemoglobin. In normal physiological states, iron is found almost exclusively bound to protein molecules in specific subcellular compartments, and the concentration of free or labile iron is very tightly controlled. When decompartmentalized, however, iron can contribute to the development of pathophysiological states through various mechanisms. One pathophysiological state that can result from increased concentrations of free iron is bacterial infection. Iron is an element that is essential for bacterial growth, and the normal homeostatic mechanism of combating bacterial infection is to create a state of hypoferremia. In the presence of increased concentrations of free iron, the probability of rapid bacterial growth greatly increases, possibly resulting in sepsis. A second state of pathophysiology that can arise from high concentrations of free iron is related to the ability of iron to catalyze free radical reactions that can cause considerable damage to cellular constituents. Iron is a transition element that normally participates in oxidative and reductive reactions, but its reactivity is directed and controlled by protein molecules. The redox activity of iron, however, can continue in solution in a nonspecific or site-specific but uncontrolled fashion, potentially damaging proteins, nucleic acids, and lipids. Such cellular damage is mediated by highly reactive oxygen-free radicals, possibly the hydroxyl radical, generated through the iron-catalyzed Haber-Weiss reaction.