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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?

A

120 days

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?

A

1-2mg/day

25
Q

What enzymes are involved in iron storage?

A

(1) FERROXIDASE: Fe2+ –> Fe3+

(2) FERROREDUCTASE: Fe3+ –> Fe2+

26
Q

What is the (practical) difference between Fe2+ and Fe3+ (once absorbed)?

A

Fe2+ = Ferrous iron = soluble storm for TRANSPORT

Fe3+ = Ferric iron = insoluble (immobile) form for STORAGE

27
Q

What is the RETICULO-ENDOTHELIAL SYSTEM (RES)

A

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
Q

What is the % of daily iron absorption?

A

~10% is absorbed

29
Q

What are the forms of dietary iron?

A

(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
Q

How is HAEM IRON absorbed?

A

Fe-PORPHYRIN COMPLEX

31
Q

What factors influence iron absorption?

A

(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
Q

What complexes enhance Iron absorption?

A

(1) ASCORBATE (vit C)
(2) LACTATE
(3) PYRUVATE

33
Q

What complexes diminish Iron absorption?

A

(1) PHYTATES (cereals)
(2) TANNATES (tea)
(3) OXALATES (rhubarb, parsley)

34
Q

Why is it difficult to get adequate absorption of iron if you are a vegetarian?

A

Vegetable iron (non-haem iron) is often complexed with tannins, phytates and/or oxalates which reduce iron absorption.

35
Q

Outline FREE IRON (non-haem) absorption bound to TRANSFERRIN

A

(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
Q

Outline Free iron (non-ahem) absorption by DCT1

A

(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
Q

Outline absorption/handling of HAEM IRON

A

(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
Q

Intracellular storage of iron

A

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
Q

How is plasma iron concentration regulated?

A

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
Q

What is the lifespan of intestinal cells in the duodenum?

A

3-10 days

41
Q

How do body iron stores affect intestinal iron absorption?

A

IREG1 (ferroportin), iron exporter, expressed on basal surface of enterocytes in duodenum.

Regulated by: HEPCIDIN (turns off IREG1)

42
Q

HEPCIDIN

A

Regulates iron absorption, used to regulate plasma Fe2+
Produced in liver
Binds to Ferroportin/IREG1 & turns off its expression = reduces plasma iron

43
Q 
what is HAEMOCHROMATOSIS
What mutation(s) cause it?
A

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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