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Physiology 3003 > Lecture 12 ---IRON METABOLISM > Flashcards

Lecture 12 ---IRON METABOLISM Flashcards

1
Q

How is iron distributed throughout the body

A

(1) HAEMOGLOBIN +++++++++++++++++
(2) Myoglobin +++
(3) Iron enzymes ++
(4) Storage Iron ++++++
(5) Transport Iron +

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2
Q

What is the total amount of iron in the body?

?? (in 60kg woman)
?? (in 70g man)

A

2300mg (in 60kg woman)

3500mg (in 70g man)

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3
Q

What is the role of haemoglobin & myoglobin?

A

Oxygen transport

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4
Q

Why do muscles need their own iron-carrying compound (myoglobin)?

A

Because they are BIG, O2 HUNGRY cells

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5
Q

What are IRON ENZYMES

A

=CATALYSTS

Cofactors in enymatic reactions, esp in redox reactions

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6
Q

What is an example of an iron enzyme?

A

Enzyme: RIBONUCLEOTIDE REDUCTASE
Source: Cytoplasm, all cells
Reaction: Ribonucleotide–> deoxyribonucleotide
Form of iron: 2Fe

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7
Q

How is iron transported and stored?

A

transported/storaged BOUND TO PROTEINS to SEQUESTER its REACTIVITY

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8
Q

Why is iron transported/stored complexed to proteins?

A

To SEQUESTER its REACTIVITY

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9
Q

What are the two redox states of Iron?

A

Fe2+ –Ferrous iron

Fe3+ –Ferric iron

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10
Q

What’s the FENTON REACTION

A

Fe2+ + H2O2 (PEROXIDE) –> Fe3+ + OH- + HYDROXYL RADICAL (OH*)

Fe3+ + PEROXIDE –> Fe2+ + H+ + HYPEROXYL RADICAL (OOH*)

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11
Q

What is produced from Fe2+ in the Fenton reaction

A

HYDROXYL RADICAL (OH*)

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12
Q

What is produced from Fe3+ in the Fenton reaction?

A

HYPEROXYL RADICAL (OOH*)

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13
Q

PEROXIDE (from the fenton reaction) is released from….

A

Mitochondria/electron transport chain

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14
Q

Name the Iron binding proteins

A

(1) TRANSFERRIN
(2) MOBILFERRIN
(3) FERRITIN

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15
Q

TRANSFERRIN…
Location:
Function:

A

Iron binding protein
>Location: predominantly OUTSIDE CELLS
–Secreted into GIT & blood
>Function: used to absorb Fe and transport around the body

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16
Q

MOBILIFERRIN…
Location:
Function:

A

Iron binding protein
>Location: exclusively INSIDE CELLS
>Function: Stopping redox damage from iron inside cells

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17
Q

FERRETIN
Location:
Function:

A

Iron Binding protein…
>Location: Mostly INSIDE cells
>Function: STORAGE

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18
Q

How is iron stored?

A

Stored in the LIVER
in either
(1) the ACCESSIBLE POOL (Fe3+ complexed to ferritin)
or;
(2) the DEAD-END POOL (at high [ferritin] coagulates –> HAEMOSIDERIN precipitate, immobile form, cell dies)

19
Q

What is HAEMOSIDERIN

A 
At high concentrations of iron 
Ferritin coagulates and forms the HAEMOSIDERIN precipitate 
= Immobile form 
= cannot be drawn on 
= cell dies 
Is a way of getting rid of excess iron
20
Q

How does iron recycling work?

A

Through the RETICULO-ENDOTHELIAL SYSTEM (RES)—RBC production= RBC destruction

(1) the MOBILE IRON POOL (in plasma) is drawn upon to SYNTHESISE ERYTHROCYTES (Red blood cells; RBC) in bone marrow. (-20mg/day)
(2) RBC lives ~120 days then broken down by MACROPHAGES IN THE SPLEEN (=+20mg/day)

21
Q

How much iron is used per day (average male) to synthesise red blood cells?

A

20 mg/day (average male)

22
Q

What is the life-span of a red blood cell?

23
Q

How much Iron is re-claimed/recycled from erythrocytes every day (average male)?

A

20mg/day (average male)

24
Q

How much Iron do we absorb from the diet every day?

25
What enzymes are involved in iron storage?
(1) FERROXIDASE: Fe2+ --> Fe3+ | (2) FERROREDUCTASE: Fe3+ --> Fe2+
26
What is the (practical) difference between Fe2+ and Fe3+ (once absorbed)?
Fe2+ = Ferrous iron = soluble storm for TRANSPORT Fe3+ = Ferric iron = insoluble (immobile) form for STORAGE
27
What is the RETICULO-ENDOTHELIAL SYSTEM (RES)
Rate of red blood cell (RBC) synthesis (in bone marrow)= rate of RBC destruction (by macrophages in spleen) = The Iron from the RBCs are RECYCLED
28
What is the % of daily iron absorption?
~10% is absorbed
29
What are the forms of dietary iron?
(1) HAEM IRON (animal form): readily absorbed via the Fe-PORPHYRIN COMPLEX (2) NON-HAEM IRON (plant form): >needs to be modified to be absorbed >either Fe2+ or Fe3+ form >Fe3+ is insoluble and CANNOT BE ABSORBED
30
How is HAEM IRON absorbed?
Fe-PORPHYRIN COMPLEX
31
What factors influence iron absorption?
(1) Digestabilibty ... (influenced by complexes) - some complexes enhance & some diminish absorption (2) The REDOX STATE...(influenced by pH) Can only absorb soluble minerals, Fe3+ is INSOLUBLE .: only Fe2+ can be absorbed.
32
What complexes enhance Iron absorption?
(1) ASCORBATE (vit C) (2) LACTATE (3) PYRUVATE
33
What complexes diminish Iron absorption?
(1) PHYTATES (cereals) (2) TANNATES (tea) (3) OXALATES (rhubarb, parsley)
34
Why is it difficult to get adequate absorption of iron if you are a vegetarian?
Vegetable iron (non-haem iron) is often complexed with tannins, phytates and/or oxalates which reduce iron absorption.
35
Outline FREE IRON (non-haem) absorption bound to TRANSFERRIN
(1) Duodenum: Fe2+ + TRANSFERRIN => Fe2+/Tf complex (2) Plasma membane: Fe2+/Tf + Tf RECEPTOR=> Endocytosed to vesicle in cytoplasm. (3) Cytoplasm: Fe2+/Tf/TfR acidified => Tf/TfR complex = recycled => Free Fe2+ is liberated (4) Free Fe2+ + MOBILIFERRIN = mobiliferrin/Fe2+ complex (5) Delivery of Fe2+ to FERROPORTIN (IREG1) on basal surface (6) released to plasma Fe2+ + free TRANSFERRIN ***SUMMARISED: Fe2+ + Transferrin(duodenum) --> Tf Receptor --> Mobilferrin (cytoplasm) --> IREG1/ferroportin (basal surface) --> Transferrin
36
Outline Free iron (non-ahem) absorption by DCT1
(1) Duodenum/plasma membrane: Binds to DCT1 DCT1: DIVALENT CATION TRANSPORTER-1 (can only transport divalent ions, i.e. Fe2+) Requires pH gradient (co-transport of Fe2+ & a proton) (2) Cytoplasm: binds to MOBILFERRIN (3) Basal surface: FERROPORTIN (IREG1) (4) Plasma: Binds to free TRANSFERRIN
37
Outline absorption/handling of HAEM IRON
(1) HAEM CARRIER PROTEIN 1 (HCP1) (duodenum) (2) HAEM OXYGENASE (enzyme) liberates Fe3+ from harm (cytoplasm) 3) Fe3+ ==reduced==> Fe2+ (cytoplasm) 4) Bound to MOBILFERRIN (cytoplasm) 5) IREG1/FERROPORTIN (basal membrane) 6) binds to free TRANSFERRIN
38
Intracellular storage of iron
EITHER ... (1) as an ACCESSIBLE POOL (Fe3+ complexed to ferritin) (enzymes: FERROXIDASE (Fe2+-->Fe3+) and FERRODUCTASE (Fe3+-->Fe2+) OR (2) DEAD END POOL (High levels of ferritin coagulate and precipitate as HAEMOSIDERIN which kills the cell)
39
How is plasma iron concentration regulated?
By regulating ABSORPTION of iron --> Expression of IREG1 on basal surface (when [Fe] are too high: (1) transcription of IREG1 is turned off => (2) LABILE IRON POOL builds up in cell => (3) [Fe] is complexed to FERRITIN for storage=> (4) high [ferritin] precipitates as HAEMOSIDERIN => (5) haemosiderin KILLS THE CELL Intestinal cells live 3-10 days, and are 'sloughed off' and passed out in the faeces
40
What is the lifespan of intestinal cells in the duodenum?
3-10 days
41
How do body iron stores affect intestinal iron absorption?
IREG1 (ferroportin), iron exporter, expressed on basal surface of enterocytes in duodenum. Regulated by: HEPCIDIN (turns off IREG1)
42
HEPCIDIN
Regulates iron absorption, used to regulate plasma Fe2+ Produced in liver Binds to Ferroportin/IREG1 & turns off its expression = reduces plasma iron
43
``` what is HAEMOCHROMATOSIS What mutation(s) cause it? ```
Iron overload disease Genes involved..(mutation) (1) HFE gene: means liver loses capacity to respond to plasma [Fe] (HFE regulates FEEDBACK...high [Fe]-->HEPCIDIN --> IREG1) (2) HAMP gene: encodes hepcidin (3) TfR2 (transferrin receptor 2) (4) HJV: haemojuvelin

Physiology 3003 (15 decks)

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