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Slide1
Iron Metabolism
© 2011 Vifor PharmaNon-commercial use permitted for training purposes in unaltered form with indication of source.www.ironatlas.com
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
3000 - 4000 mgSlide2
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
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide3
Iron Metabolism
- Absorption
RegulATION OF IRON aBSORPTION
DMT-1
Dcytb
Transferrin
Hephaestin
Ferroportin
HCP-1Ferritin
Fe(III)
Fe(II)
Haem iron
Hepcidin
1
2
3
4
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide4
TRANSPORT
Iron Metabolism -
Transport
DMT-1
Transferrin
Hephaestin
Ferroportin
Transferrin receptor
Fe(III
)
Fe(II
)
Apotransferrin
ENTEROCYE
CONSUMER CELL
1
2
3
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide5
USAGE
CONSUMER CELL
Iron Metabolism - Usage
© 2011 Vifor Pharma
Non-commercial use permitted for training purposes in unaltered form with indication of source.
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CONSUMER CELL
Apotransferrin
Transferrin
receptor
DMT-1
Transferrin
Fe
(II)
Mitochondrium
Ferritin
H+
1
2
3
4
5
Slide6
USAGE
ERYTHROPOIESIS
Iron Metabolism
- Usage
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes in unaltered form with indication of source.
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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
d
ays
EPO dependence
10-13 days
Iron dependence
3-4 days
1
2
3Slide7
USAGE
RESPIRATORY CHainIron Metabolism - Usage
C
omplex
III
Cytochrome-c-Reductase
C
omplex INADH-Dehydrogenase
Complex
IISuccinate-Dehydrogenase
Complex IV
Cytochrome-c-Oxidase
Complex VATP-
Synthase
Enzymes with Heme iron
Enzymes with Iron-Sulfur Clusters
Interstitial space
Mitochodrial Matrix
e
-
H
+
e
-
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide8
USAGE
Oxidative stressIron Metabolism - Usage
IRON-OVERLOADED CELL
Lysosome
O
2
Fe
(II)
Ferritin
H
2
O
2
Mitochondrium
Haemosiderin
H
2
O
Fenton’s
reaction: Fe(II) +
H
2
O
2
HO
•
Fe(III) + HO–
+ HO•
Fe(III)
1
2
3
4
5
6
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide9
LOSS
Iron Metabolism - Loss
SKIN- / MUCOSA- CELL
Transferrin
Apotransferrin
ERYTHROCYTE
1
2
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2011 Vifor Pharma
Non-commercial use permitted for training purposes
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www.ironatlas.comSlide10
recYcling
Iron Metabolism
- Recycling
SPLEEN
MACROPHAGE
IN THE SPLEEN
ERYTHROCYTE
Caeruloplasmin
Transferrin
Ferroportin
Haemosiderin
Ferritin
Fe(III)
Fe(II)
LIP
1
2
3
4
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide11
Storage
Iron Metabolism
- Storage
Caeruloplasmin
Transferrin
Ferroportin
Haemosiderin
Ferritin
Fe(III)
Fe(II)
LIP
Transferrin
receptor
Apotransferrin
KUPFFER CELL
OF
THE
LIVERERYTHROCYTE
1
2
3
©
2011 Vifor Pharma
Non-commercial use permitted for training purposes
in unaltered form with indication of source.
www.ironatlas.comSlide12
REGULation
AT IRON DEFICIENCY
Iron Metabolism - Regulation
© 2011 Vifor Pharma
Non-commercial use permitted for training purposes in unaltered form with indication of source.
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HEPATOCYTE
Caeruloplasmin
Transferrin
Ferroportin
Ferritin
Fe(II)
LIP
Transferrin
receptor
IRP
1
Slide13
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.
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HEPATOCYTE
Caeruloplasmin
Transferrin
Ferroportin
Ferritin
Fe(II)
LIPTransferrin receptor
IRP
Hepcidin
Ferroportin
Fe(II)
1
2
3
4
Slide14
Iron Metabolism - Tables
© 2011 Vifor PharmaNon-commercial use permitted for training purposes in unaltered form with indication of source.www.ironatlas.comSlide15
Iron Metabolism - Tables
© 2011 Vifor PharmaNon-commercial use permitted for training purposes in unaltered form with indication of source.www.ironatlas.comSlide16
LEGAL Notice
Iron Metabolism© 2011 Vifor PharmaNon-commercial use permitted for training purposes in unaltered form with indication of source.
www.ironatlas.com
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
,
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,
Lucerne
Realisation IronAtlas
:
Monokel Games GmbH
,
Zurich
Project
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
.
©
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
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may be
used for non-commercial educational purposes
in unaltered form under
indication of the reference
(
www.ironatlas.com
).
Further
information
:
www.ironatlas.com
C
ontact
:
info@ironatlas.comSlide17
Iron Metabolism
© 2011 Vifor PharmaNon-commercial use permitted for training purposes in unaltered form with indication of source.www.ironatlas.com
Table of Elements
Caeruloplasmin
Duodenal 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
O
2
C
atalase
Hydroxyl radical
IRON IONS
STORED IRON
CHANNEL PROTEINS
TRANSPORTPROTEINE
Reductases / oxidases
REGULATORY PROTEINS
FeS-Cluster