Iron Metabolism Flashcards

1
Q

State three biological processes that are reliant on iron.

A

oxygen transport, DNA synthesis, electon transport

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2
Q

(a) Dietary iron can exist in two forms: ____________.
(b) Which is more readily absorbed?

A

(a) heme iron [found in animal products] and non-heme iron [found in plant-based foods]
(b) Heme iron is more readily absorbed.

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3
Q

Briefly explain the haem pathway of iron absorption.

A

✓ Haem is absorbed into enterocyte as intact metalloprotein through specific receptors. It is taken up by enterocytes (intestinal cells) via a specific receptor known as the heme carrier protein 1 (HCP1) or heme transporter.
✓ Once inside the enterocyte, the heme molecule is broken down by the enzyme heme oxygenase.
✓ Heme Oxygenase: This enzyme cleaves the heme ring to release ferrous iron (Fe²⁺), biliverdin, and carbon monoxide.
✓ The released ferrous iron can then be utilized by the body, stored as ferritin within the enterocyte, or exported into the bloodstream via ferroportin.
[Diagram 1] [Diagram 2] [Diagram 3]

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4
Q

Outline the non-haem pathway of iron absorption.

A

(1) Non-heme iron exists in both ferric (Fe³⁺) and ferrous (Fe²⁺) forms. Ferric iron must be reduced to ferrous iron before absorption.

(2) This reduction is faciliated by duodenal cytochrome B reductase (DcytB) on the apical surface of enterocytes, with the help of reducing agents like vitamin C and the acidic environment provided by stomach HCl.

(3) Ferrous iron is then transported into enterocytes via the divalent metal transporter 1 (DMT1).

[Diagram 1] [Diagram 2]

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5
Q

Explain the role of hephaestin in iron metabolism.

A

Hephaestin is a transmembrane protein that is primarily expressed in the enterocytes of the small intestine, particularly in the villi where iron absorption occurs.
It acts as a copper-dependent ferroxidase, converting ferrous iron (Fe²⁺) to ferric iron (Fe³⁺). This oxidation is crucial because ferric iron is the form that can be transported in the bloodstream. [Diagram 1] [Diagram 2]

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6
Q

List three biochemicals that enhance the absoption of non-heme iron.

A

ascorbic acid (vitamin C), amino acids, organic acids, simple sugars, cysteine

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7
Q

List three biochemicals that inhibit the absoption of non-heme iron.

A

phosphates, polyphenols, phytates, calcium, zinc, tanin

Further notes:
What are phytates?
Phytates, also known as phytic acid, are naturally occurring compounds found in plant seeds. They serve as the primary storage form of phosphorus in many plants.
Found in: Phytates are present in a variety of plant-based foods, including grains, legumes, nuts and seeds.
Anti-nutrient properties: Phytates are often referred to as “anti-nutrients” because they can bind to essential mineral such as iron, zinc, calcium, and magnesium, reducing their absorption in the digestive tract.

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8
Q

Hepcidin is a key hormone in the regulation of iron homeostasis, often referred to as the “master iron regulator”. Where is it produced?

A

liver

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9
Q

Explain the mechanism of action of hepcidin.

A

➤ Hepcidin exerts its effects by binding to ferroportin, the only known iron exporter located on the surface of enterocytes, macrophages, and hepatocytes.
➤ When hepcidin binds to ferroportin, it triggers the internalization and degradation of ferroportin. This process reduces the amount of iron released into the bloodstream from these cells.

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10
Q

What effect does hepcidin have on intestinal iron absorption?

A

Hepcidin decreases the absorption of dietary iron from the intestine by degrading ferroportin on enterocytes.

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11
Q

How does hepcidin affect iron recycling?

A

Hepcidin reduces the release of iron from macrophages that recycle iron from senescent red blood cells.

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12
Q

How does erythropoietic activity influence hepcidin levels?

A

Increased erythropoietic activity, such as during anemia or hypoxia, decreases hepcidin levels to allow more iron to be available for red blood cell production.

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13
Q

What triggers the production of hepcidin?

A

Hepcidin production is upregulated in response to increased iron levels and inflammation. [Diagram 1] [Diagram 2]

Further notes:
By reducing the availability of iron in the bloodstream, the body limits the resources available to these pathogens, helping to control the infection.

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14
Q

What is the primary protein responsible for transporting iron in the plasma?

A

transferrin

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15
Q

In what form does transferrin bind to iron?

A

Ferric form (Fe3+)

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16
Q

How do cells take up iron from the plasma?

A

Through transferrin receptors on their surface, internalizing the transferrin-iron complex via endocytosis.

Further notes:
☛ Cells have transferrin receptors (TfR1) on their surface. The transferrin-iron complex binds to these receptors.
This binding triggers endocytosis, where the cell membrane engulfs the transferrin-iron complex, forming an endosome.
☛ Inside the endosome, the acidic environment causes transferrin to release the iron.
☛ The iron is then reduced from Fe3+ to Fe2+ by endosomal reductases.
☛ The released iron is transported out of the endosome into the cytoplasm by divalent metal transporter 1 (DMT1).
☛ The transferrin receptor and the now iron-free transferrin (apotransferrin) are recycled back to the cell surface. Apotransferrin is recycled back into the plasma to bind more iron.
[Diagram]

17
Q

In what forms is iron stored in the liver, spleen, and bone marrow?

A

Ferritin or hemosiderin

18
Q

(a) Is ferritin water soluble or insoluble?
(b) What are the components of ferritin?
(c) Where is ferritin found in the body?
(d) What does plasma ferritin content indicate?

A

(a) Water soluble
(b) Ferritin is composed of ferric hydroxide (Fe(OH)₃) and apoferritin.
(c) Ferritin is found in all body cells and tissue fluids, including the liver, spleen, bone marrow, and muscles.
(d) Plasma ferritin content closely correlates with the body’s iron stores.

19
Q

(a) Where is haemosiderin primarily located?
(b) Is haemosiderin water soluble or insoluble?
(c) Under what conditions can haemosiderin pathologically accumulate in tissues?

A

(a) Hemosiderin is primarily found in the macrophage system, including bone marrow, Kupffer cells in the liver, and the spleen.
(b) Water insoluble
(c) Haemosiderin can pathologically accumulate in tissues in conditions like hemochromatosis or after hemorrhage.

Further notes:
Hemochromatosis
✓ Definition: Hemochromatosis is a genetic disorder characterized by excessive absorption of dietary iron, leading to iron overload in the body.
✓ Mechanism: In hemochromatosis, the body’s regulatory mechanisms for iron absorption are impaired, causing iron to accumulate in various organs.
✓ Pathological Accumulation: Excess iron is stored as haemosiderin in tissues such as the liver, heart, pancreas, and joints. This can lead to tissue damage and organ dysfunction.

20
Q

Which stain is used to show iron stores in tissues?

A

Perl’s stain aka. the Prussian blue reaction
[Slide 1] [Slide 2] [Slide 3]

21
Q

Which special stain is used to demonstrate hemosiderin pigment in the liver?
(a) Prussian blue stain
(b) Periodic acid Schiff stain
(c) Sudan black B stain
(d) Trichrome stain
(e) Oil red O stain

A

(a) Prussian blue stain

22
Q

Which of the following is an enhancer of iron absorption in the small intestines?
(a) Calcium
(b) Phosphates
(c) Oxalates
(d) Phytates
(e) Ascorbic acid

A

(e) Ascorbic acid

23
Q

Iron overload is usually associated with ____________.
(a) decreased plasma iron
(b) increased plasma transferrin
(c) pernicious anaemia
(d) increased total iron binding capacity
(e) increased plasma ferritin

A

(e) increased plasma ferritin

24
Q

The site of maximum absorption of iron is the ____________.
(a) stomach
(b) terminal ileum
(c) duodenum
(d) caecum
(e) distal ileum

A

(c) duodenum

25
Q

Dietary sources rich in iron do not include ____________.
(a) egg yolk
(b) milk
(c) fatty meat
(d) green vegetables
(e) liver

A

(b) milk