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

http://www.ironatlas.com/


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





Iron Metabolism - Absorption

REGULATION OF IRON ABSORPTION

DMT-1

Dcytb

Transferrin

Hephaestin

Ferroportin

HCP-1

Ferritin

Fe(III) Fe(II)

Haem iron

Hepcidin12

34





TRANSPORT

Iron Metabolism - Transport

DMT-1

Transferrin

Hephaestin

Ferroportin

Transferrin receptor

Fe(III)Fe(II)

Apotransferrin

ENTEROCYE

CONSUMER CELL

1

2

3





USAGECONSUMER CELL

Iron Metabolism - Usage

CONSUMER CELLApotransferrin

Transferrin receptor

DMT-1

Transferrin

Fe(II)

MitochondriumFerritin

H+

1 2

3

4

5





USAGEERYTHROPOIESIS


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





USAGERESPIRATORY CHAIN


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-





USAGEOXIDATIVE STRESS


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





LOSS

Iron Metabolism - Loss

SKIN- / MUCOSA- CELL

Transferrin

Apotransferrin

ERYTHROCYTE

1

2





RECYCLING

Iron Metabolism - Recycling

SPLEEN

MACROPHAGE IN THE SPLEEN

ERYTHROCYTE

Caeruloplasmin

Transferrin

Ferroportin

Haemosiderin

Ferritin

Fe(III)

Fe(II)

LIP

1

2

3

4





STORAGE

Iron Metabolism - Storage

Caeruloplasmin

Transferrin

FerroportinHaemosiderin

Ferritin

Fe(III)

Fe(II)

LIP

Transferrinreceptor

Apotransferrin KUPFFER CELL OF THE LIVER

ERYTHROCYTE

1

2

3





REGULATIONAT IRON DEFICIENCY

Iron Metabolism - Regulation

HEPATOCYTE

Caeruloplasmin

Transferrin

Ferroportin

Ferritin

Fe(II)

LIP

Transferrinreceptor

IRP

1





REGULATIONAT HIGH IRON CONCENTRATION

Iron Metabolism - Regulation

HEPATOCYTE

Caeruloplasmin

Transferrin

Ferroportin

Ferritin

Fe(II)

LIP

Transferrin receptorIRP

Hepcidin

Ferroportin

Fe(II)

1

2

34





Iron Metabolism - Tables





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

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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





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