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Transcript of Iron Metabolism © 2015 Vifor Pharma Non-commercial use permitted for training purposes in unaltered...
Iron Metabolism
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
STORAGETRANSPORT
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 iron3000 - 4000 mg
ABSORPTION
Iron Metabolism - Absorption
ENTEROCYTE
APICAL
BASOLATERAL
DMT-1
Dcytb
Transferrin
Hephaestin
Ferroportin
HCP-1
Ferritin
Fe(III)Fe(II)
Haem iron
Apotransferrin
1
2
3 4
5
6
7
8
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
Iron Metabolism - Absorption
REGULATION OF IRON ABSORPTION
DMT-1
Dcytb
Transferrin
Hephaestin
Ferroportin
HCP-1
Ferritin
Fe(III) Fe(II)
Haem iron
Hepcidin12
34
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
TRANSPORT
Iron Metabolism - Transport
DMT-1
Transferrin
Hephaestin
Ferroportin
Transferrin receptor
Fe(III)Fe(II)
Apotransferrin
ENTEROCYE
CONSUMER CELL
1
2
3
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
USAGECONSUMER CELL
Iron Metabolism - Usage
CONSUMER CELLApotransferrin
Transferrin receptor
DMT-1
Transferrin
Fe(II)
MitochondriumFerritin
H+
1 2
3
4
5
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
USAGEERYTHROPOIESIS
Iron Metabolism - Usage
Apotransferrin
EPOEPO-Receptor
Transferrin
Fe(II)Transferrinreceptor
Haem iron
STEM CELL
BFU-ERYTHROID
CFU-ERYTHROID
PRO-ERYTHROBLAST
ERYTHROBLAST
RETIKULOCYTE
ERYTHROCYTE
Durationof erythropoiesisapprox. 23 days
EPO dependence10-13 days
Iron dependence3-4 days
1
2
3
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
USAGERESPIRATORY CHAIN
Iron Metabolism - Usage
Complex IIICytochrome-c-Reductase
Complex INADH-Dehydrogenase
Complex IISuccinate-Dehydrogenase
Complex IVCytochrome-c-Oxidase
Complex VATP-Synthase
Enzymes with Heme iron
Enzymes with Iron-Sulfur Clusters
Inte
rstit
ial s
pace
Mito
chod
rial M
atrix
e-
H+
e-
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
USAGEOXIDATIVE STRESS
Iron Metabolism - Usage
IRON-OVERLOADED CELL
Lysosome
O2
Fe(II)
Ferritin
H2O2
MitochondriumHaemosiderin
H2O
Fenton’s reaction: Fe(II) + H2O2
HO•
Fe(III) + HO–+ HO•
Fe(III)
1
2
34
5
6
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
LOSS
Iron Metabolism - Loss
SKIN- / MUCOSA- CELL
Transferrin
Apotransferrin
ERYTHROCYTE
1
2
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
RECYCLING
Iron Metabolism - Recycling
SPLEEN
MACROPHAGE IN THE SPLEEN
ERYTHROCYTE
Caeruloplasmin
Transferrin
Ferroportin
Haemosiderin
Ferritin
Fe(III)
Fe(II)
LIP
1
2
3
4
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
STORAGE
Iron Metabolism - Storage
Caeruloplasmin
Transferrin
FerroportinHaemosiderin
Ferritin
Fe(III)
Fe(II)
LIP
Transferrinreceptor
Apotransferrin KUPFFER CELL OF THE LIVER
ERYTHROCYTE
1
2
3
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
REGULATIONAT IRON DEFICIENCY
Iron Metabolism - Regulation
HEPATOCYTE
Caeruloplasmin
Transferrin
Ferroportin
Ferritin
Fe(II)
LIP
Transferrinreceptor
IRP
1
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
REGULATIONAT HIGH IRON CONCENTRATION
Iron Metabolism - Regulation
HEPATOCYTE
Caeruloplasmin
Transferrin
Ferroportin
Ferritin
Fe(II)
LIP
Transferrin receptorIRP
Hepcidin
Ferroportin
Fe(II)
1
2
34
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
Iron Metabolism - Tables
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
Iron Metabolism - Tables
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
LEGAL NOTICE
Iron Metabolism
REFERENCES
Hentze M, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117(3): 285-97.
Ganz T. Molecular control of iron transport. J Am Soc Nephrol 2007; 18(2): 394-400.
Andrews NC. Forging a field: the golden age of iron biology. Blood 2008; 112(2): 219-30.
Demarmels-Biasiutti F. Die Regulation des Eisenstoffwechsels – neue Erkenntnisse. Schweiz Med Forum 2009; 9(36): 630-2.
Nemeth E. Iron regulation and erythropoiesis. Curr Opin Hematol 2008; 15(3): 169-75.
Martius F. Eisenmangel ohne Anämie – ein heisses Eisen?. Schweiz Med Forum 2009; 9(15-16): 294-9.
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): 4617-26.
Zhang AS, Enns CA. Molecular mechanisms of normal iron homeostasis. HematologyAm Soc Hematol Educ Program 2009; 207-14.
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): 997-1030.
Andrews NC.. Disorders of iron metabolism. New Engl J Med 1999; 341(26): 1986-1995.
This content was created with expert assistance from:
Dr. med. Rudolf Benz, Kantonsspital Münsterlingen, SwitzerlandProf. Dr. med. Andreas Huber, Kantonsspital Aarau, SwitzerlandDr. med. Franziska Demarmels-Biasiutti, Inselspital Bern, SwitzerlandProf. Dr. med. Jean-Michel Gaspoz, HUG, SwitzerlandDr. med. Jeroen Goede, Universitätsspital Zürich, SwitzerlandProf. Dr. Willem H. Koppenol, ETH Zürich, SwitzerlandProf. Dr. med. Wolfgang Korte, Kantonsspital St. Gallen, SwitzerlandDr. med. Paul Pugin, Hôpital cantonal de Fribourg, SwitzerlandDr. med. Kaveh Samii, HUG, SwitzerlandDr. med. Jeroen Goede, University hospital of Zürich, SwitzerlandProf. Dr. med. André Tichelli, Universitätsspital Basel, SwitzerlandProf. Dr. med. Gérard Waeber, CHUV, Lausanne, SwitzerlandProf. Dr. Dr. med. Walter A. Wuillemin, Kantonsspital Luzern, Switzerland
Design: descience - A. Ulrich & N. Stadelmann, LucerneRealisation IronAtlas: Monokel Games GmbH, ZurichProject management: Dr. Pascal Schär & Dr. Viktor Pavelic, Vifor Pharma
These presentations are a port of the IronAtlas. Usage of the IronAtlas is subject to the Terms of Use.
© 2015 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).
Further information: www.ironatlas.comContact: [email protected]
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com
Iron Metabolism
TABLE OF ELEMENTS
CaeruloplasminDuodenal cytochrome B(Dcytb)
Hephaestin Hepcidin iron-regulating proteins(IRP)
Erythropoietin(EPO)
Haem carrier protein 1(HCP-1)
Divalent metal transporter 1
(DMT-1)
Ferroportin Apotransferrin Transferrin Transferrin receptor(TfR)
Fe(II)Fe(III) Haem iron H+ Ferritin Haemosiderin
O2Catalase Hydroxyl radical
IRON IONS STORED IRON
CHANNEL PROTEINS TRANSPORTPROTEINE
REDUCTASES / OXIDASES REGULATORY PROTEINS
FeS-Cluster
© 2015 Vifor PharmaNon-commercial use permitted for training purposes
in unaltered form with indication of source.www.ironatlas.com