Hemoglobin. A biologic fenton reagent.
Iron and iron compounds may facilitate hydroxyl-radical generation from activated oxygen species. Earlier work on the generation of this radical has been focused on simple, low-molecular-weight iron compounds. We hypothesized that free hemoglobin, like other iron-rich substances, might also mediate hydroxyl-radical generation. We find: 1) In the presence of a superoxide anion-generating system (hypoxanthine and xanthine oxidase), hemoglobin promotes hydroxyl-radical formation in a dose-dependent fashion. 2) This generation of hydroxyl radical is greatly decreased by prior oxidation of the hemoglobin, equilibration of hemoglobin with carbon monoxide, or addition of catalase, while added superoxide dismutase has little effect. Therefore, hydroxyl radical probably arises primarily via reaction between the ferrous heme iron and H2O2. 3) In further support of this, hydroxyl radical forms as readily upon the addition of H2O2 to hemoglobin. 4) Hemoglobin also increases hypoxanthine/xanthine oxidase-driven peroxidation of poly-unsaturated fatty acids such as arachidonic acid and human red cell membrane lipids. 5) The addition of sufficient haptoglobin (the plasma hemoglobin-binding protein) suppresses both hemoglobin-driven hydroxyl radical and malondialdehyde generation. Thus, free hemoglobin may be biologically hazardous, in part because it acts as a "Fenton" reagent, having the potential to catalyze hydroxyl-radical generation in areas of inflammation. Haptoglobin, which binds hemoglobin very tightly, blocks this through a presently unknown mechanism. An important physiologic function of haptoglobin may be prevention of such hemoglobin-mediated oxidation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005609:Free Radicals; D006420:Hemeproteins / Q000378:metabolism; D006441:Hemoglobin A / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006878:Hydroxides / Q000097:blood; D017665:Hydroxyl Radical; D007501:Iron; D007700:Kinetics; D046911:Macromolecular Substances; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005609:Free Radicals; D006420:Hemeproteins; D006454:Hemoglobins; D006878:Hydroxides; D046911:Macromolecular Substances; D016718:Arachidonic Acid; D017665:Hydroxyl Radical; D006441:Hemoglobin A; D007501:Iron