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Iron Metabolism © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. www.ironatlas.com STORAGE.

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Presentation on theme: "Iron Metabolism © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. www.ironatlas.com STORAGE."— Presentation transcript:

1 Iron Metabolism © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. STORAGE TRANSPORT REGULATION USAGE LOSS RECYCLING ABSORPTION ~ 300 mg 1-2 mg/d 25 mg/d 3 mg ~ 1000 mg ~ 600 mg 1-2 mg/d ~ 300 mg ~ 1800 mg Total body iron mg

2 ABSORPTION Iron Metabolism - Absorption ENTEROCYTE APICAL BASOLATERAL DMT-1 Dcytb Transferrin Hephaestin Ferroportin HCP-1 Ferritin Fe(III) Fe(II) Haem iron Apotransferrin © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

3 Iron Metabolism - Absorption REGULATION OF IRON ABSORPTION DMT-1 Dcytb Transferrin Hephaestin Ferroportin HCP-1 Ferritin Fe(III) Fe(II) Haem iron Hepcidin © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

4 TRANSPORT Iron Metabolism - Transport DMT-1 Transferrin Hephaestin Ferroportin Transferrin receptor Fe(III) Fe(II) Apotransferrin ENTEROCYE CONSUMER CELL © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

5 USAGE CONSUMER CELL Iron Metabolism - Usage © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. CONSUMER CELL Apotransferrin Transferrin receptor DMT-1 Transferrin Fe(II) Mitochondrium Ferritin H

6 USAGE ERYTHROPOIESIS Iron Metabolism - Usage © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. Apotransferrin EPO EPO-Receptor Transferrin Fe(II) Transferrin receptor Haem iron STEM CELL BFU-ERYTHROID CFU-ERYTHROID PRO-ERYTHROBLAST ERYTHROBLAST RETIKULOCYTE ERYTHROCYTE Duration of erythropoiesis approx. 23 days EPO dependence days Iron dependence 3-4 days 1 2 3

7 USAGE RESPIRATORY CHAIN Iron Metabolism - Usage Complex III Cytochrome-c-Reductase Complex I NADH-Dehydrogenase Complex II Succinate-Dehydrogenase Complex IV Cytochrome-c-Oxidase Complex V ATP-Synthase Enzymes with Heme iron Enzymes with Iron-Sulfur Clusters Interstitial space Mitochodrial Matrix e-e- H+H+ e-e- © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

8 USAGE OXIDATIVE STRESS Iron Metabolism - Usage IRON-OVERLOADED CELL Lysosome O2O2 Fe(II) Ferritin H2O2H2O2 Mitochondrium Haemosiderin H2OH2O Fentons reaction: Fe(II) + H 2 O 2 HO Fe(III) + HO – + HO Fe(III) © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

9 LOSS Iron Metabolism - Loss SKIN- / MUCOSA- CELL Transferrin Apotransferrin ERYTHROCYTE 1 2 © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

10 RECYCLING Iron Metabolism - Recycling SPLEEN MACROPHAGE IN THE SPLEEN ERYTHROCYTE Caeruloplasmin Transferrin Ferroportin Haemosiderin Ferritin Fe(III) Fe(II) LIP © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

11 STORAGE Iron Metabolism - Storage Caeruloplasmin Transferrin Ferroportin Haemosiderin Ferritin Fe(III) Fe(II) LIP Transferrin receptor Apotransferrin KUPFFER CELL OF THE LIVER ERYTHROCYTE © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

12 REGULATION AT IRON DEFICIENCY Iron Metabolism - Regulation © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. HEPATOCYTE Caeruloplasmin Transferrin Ferroportin Ferritin Fe(II) LIP Transferrin receptor IRP 1

13 REGULATION AT HIGH IRON CONCENTRATION Iron Metabolism - Regulation © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. HEPATOCYTE Caeruloplasmin Transferrin Ferroportin Ferritin Fe(II) LIP Transferrin receptor IRP Hepcidin Ferroportin Fe(II)

14 Iron Metabolism - Tables © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

15 Iron Metabolism - Tables © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source.

16 LEGAL NOTICE Iron Metabolism © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. REFERENCES Hentze M, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117(3): Ganz T. Molecular control of iron transport. J Am Soc Nephrol 2007; 18(2): Andrews NC. Forging a field: the golden age of iron biology. Blood 2008; 112(2): Demarmels-Biasiutti F. Die Regulation des Eisenstoffwechsels – neue Erkenntnisse. Schweiz Med Forum 2009; 9(36): Nemeth E. Iron regulation and erythropoiesis. Curr Opin Hematol 2008; 15(3): Martius F. Eisenmangel ohne Anämie – ein heisses Eisen?. Schweiz Med Forum 2009; 9(15-16): Fehr J, Favrat B, Schleiffenbaum B, Krayenbühl PA, Kapanci C, von Orelli F. Diagnose und Behandlung von Eisenmangel ohne Anämie. Praxis 2009; 98(24): 1445–51. Wick M, Pinggera W, Lehmann P. Klinik und Labor, Eisenstoffwechsel und Anämien - Neue Konzepte bei renalen- und Tumoranämien und rheumatoider Arthritis (Siebte erweiterte Auflage). Springer Wien New York 2002; Muñoz M, Villar I, García-Erce JA. An update on iron physiology. World J Gastroenterol 2009; 15(37): Zhang AS, Enns CA. Molecular mechanisms of normal iron homeostasis. Hematology Am Soc Hematol Educ Program 2009; Crichton RR, Danielson BG, Geisser P. Iron Therapy with special emphasis on intravenous administration. Uni-Med Verlag 2008; Nielson P. Diagnostik und Therapie von Eisenmangel mit und ohne Anämie. Uni-Med Verlag 2009; MacKenzie EL, Iwasaki K, Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal 2008; 10(6): Andrews NC.. Disorders of iron metabolism. New Engl J Med 1999; 341(26): This content was created with expert assistance from: Dr. med. Rudolf Benz, Kantonsspital Münsterlingen, Switzerland Prof. Dr. med. Andreas Huber, Kantonsspital Aarau, Switzerland Dr. med. Franziska Demarmels-Biasiutti, Inselspital Bern, Switzerland Prof. Dr. med. Jean-Michel Gaspoz, HUG, Switzerland Dr. med. Jeroen Goede, Universitätsspital Zürich, Switzerland Prof. Dr. Willem H. Koppenol, ETH Zürich, Switzerland Prof. Dr. med. Wolfgang Korte, Kantonsspital St. Gallen, Switzerland Dr. med. Paul Pugin, Hôpital cantonal de Fribourg, Switzerland Dr. med. Kaveh Samii, HUG, Switzerland Dr. med. Jeroen Goede, University hospital of Zürich, Switzerland Prof. Dr. med. André Tichelli, Universitätsspital Basel, Switzerland Prof. Dr. med. Gérard Waeber, CHUV, Lausanne, Switzerland Prof. Dr. Dr. med. Walter A. Wuillemin, Kantonsspital Luzern, Switzerland Design: descience - A. Ulrich & N. Stadelmann, Lucernedescience Realisation IronAtlas: Monokel Games GmbH, Zurich Project management: Dr. Pascal Schär & Dr. Viktor Pavelic, Vifor PharmaMonokel Games GmbH These presentations are a port of the IronAtlas. Usage of the IronAtlas is subject to the Terms of Use.Terms of Use © 2011 Vifor Pharma. All rights reserved. Reproduction, publication or distribution (in full or in part) is only permitted with the prior written consent of Vifor Pharma. Exception: Images from the IronAtlas may be used for non-commercial educational purposes in unaltered form under indication of the reference (www.ironatlas.com).www.ironatlas.com Further information: Contact:

17 Iron Metabolism © 2011 Vifor Pharma Non-commercial use permitted for training purposes in unaltered form with indication of source. TABLE OF ELEMENTS CaeruloplasminDuodenal cytochrome B (Dcytb) HephaestinHepcidiniron-regulating proteins (IRP) Erythropoietin (EPO) Haem carrier protein 1 (HCP-1) Divalent metal transporter 1 (DMT-1) FerroportinApotransferrinTransferrinTransferrin receptor (TfR) Fe(II)Fe(III) Haem ironH+H+ FerritinHaemosiderin O2O2 CatalaseHydroxyl radical IRON IONSSTORED IRON CHANNEL PROTEINSTRANSPORTPROTEINE REDUCTASES / OXIDASES REGULATORY PROTEINS FeS-Cluster


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