Heme in Health and Disease
Under homeostasis, the reactivity of heme is controlled by its insertion into the “heme pockets” of hemoproteins. Under oxidative stress however, some hemoproteins, e.g. hemoglobin, can release their heme prosthetic groups. The non-protein-bound (free) heme produced in this manner becomes highly cytotoxic, most probably due to the Fe atom contained within its protoporphyrin IX ring, which can undergo Fenton chemistry to catalyze in an unfettered manner the production of free radicals. This property of free heme can sensitize a variety of cell types to undergo programmed cell death in response to pro-inflammatory agonists. This deleterious effect is thought to play an important role in the pathogenesis of certain inflammatory diseases such as malaria.
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