Iron Transport Flashcards
Iron Goldilocks zone

Fenton chemistry
Iron reactions with water producing free radicals
Most of the elemental iron that we eat is present in our body in the form of
rust!
Particularly rust sequestered in ferritin.

Transferrin

Ferritin

Low transferrin saturation
Iron deficiency
Overloaded transferrin saturation
iron toxicity
High serum ferritin
Ferritin is primarily a cellular protein.
However, some ferritin leaks in the blood and thus high serum ferritin can be associated with iron overload. Other diseases of the liver can also cause elevated serum ferri:n.
Major components of iron economy
60-70%: In erythrocytes as hemoglobin.
25%: In liver cells (hepatocytes and Kupffer cells) and macrophages as ferritin stores.
- 5%: In tissues
- 1%: As blood transferrin
~1% is recycled daily.
Iron steady state
Iron loss = Iron gain = 1-2 mg per day
~4g per adult male human body
Macrophage iron regulation

Intestinal Epithelium iron regulation

Reticulocyte iron regulation

DMT1
Divalent metal transporter 1

FPN1
Ferroportin 1

How is secretion of iron regulated by liver and kidneys?
It’s not!!!!!!!
Only absorption is regulated, and it is regulated on the transcriptional level (upregulation of DMT1 and FPN1) and the mRNA stability level
Why is DMT1 upregulation insufficienct to absorb iron?
Without FPN1 upregulation as well, the iron cannot diffuse into the lamina propria in a timely manner before the enterocyte is sloughed off and the iron is lost
FPN1 expression in an iron replete vs iron deficient mouse

Duodenal iron staining in an iron replete vs iron deficient mouse
Note that in the replete condition the iron clusters in the location of the ferritin storage clusters.

Hepcidin

The human body’s iron sensor

How hepcidin regulates enterocytes
Hepcidin binds to FPN1 directly via the basolateral surface of enterocytes. It induces phosphorylation and endocytosis. The endocytosed FPN1 is ubiquitinated and targeted for lysosomal degradation (NOT proteasomal)

What controls serum iron availability?

Each maturing erythrocyte needs approximately ____ iron atoms before it is mature.
Each maturing erythrocyte needs approximately 3 billion iron atoms before it is mature.

