Hemoglobin denaturation and iron release in acidified red blood cell lysate--a possible source of iron for intraerythrocytic malaria parasites.
Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of hemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, its rate decreasing with increasing pH, and increasing in presence of protease. Although the pH- and proteolysis-dependent release of iron paralleled Hb denaturation, released iron accounted for only a few percent of degraded Hb. Superoxide dismutase, catalase, and various scavengers of oxidative radicals had no effect on either process, consistent with the involvement of Fe(IV) intermediates in iron release from heme. Histidine and imidazole inhibited iron release, probably by binding directly to heme. Ascorbate enhanced iron release considerably but marginally enhanced the denaturation of Hb, suggesting that redox cycling of lysate free iron accelerated further release from heme. These processes could account for the endogenous supply of iron to the malarial parasite.
Gabay
T
T
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Ginsburg
H
H
D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016166:Free Radical Scavengers; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D008288:Malaria / Q000097:blood*; D011480:Protease Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D016166:Free Radical Scavengers; D006454:Hemoglobins; D011480:Protease Inhibitors; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D010450:Endopeptidases; D002402:Cathepsin D; D001205:Ascorbic Acid