Lecture 28: Iron Metabolism Flashcards
What type of mineral is iron?
Micromineral
Compare and contrast heme-bound iron vs. non-heme bound iron?
Heme-bound Iron: Found in animal tissues, greater absorption
Non Heme-Bound Iron: Found in plants, less absorption
Main function of iron?
O2 transport
While iron ____ is tightly regulated, there is no regulation of iron ____
Absorption; excretion
In what four tissues is iron distributed in?
1) Muscle (myoglobin)
2) Bone marrow (RBC)
3) Erythrocytes (hemoglobin)
4) Liver*
5) Intestine
6) Reticuloendothelial macrophages (destroy RBC)
What organ stores iron? What oran is important for iron absorption?
Storage: The liver
Absorption: Intestinal cells (enterocytes)
Iron is utilized in the bone marrow for ____ and in RBC’s for ____
Bone marrow: RBC production
RBC’s: O2 transport
What three structures are involved in absorption of non-heme iron?
1) Duodenal Cytochrome B: converts non-heme iron to Fe3+ to Fe2+ (Vit C required!)
2) DMT1: Transport iron into intestinal cell (enterocyte)
3) Ferritin(Fe3+): stores iron
What three structures are involved in absorption of heme-containing iron?
1) Heme Carrier Protein: allows iron to be transported into enterocyte (intestine cells)
2) Heme Oxygenase: breaks iron out of heme group, resulting in free iron
3) Ferritin: stores iron
What structure is the main intracellular structure for storing iron?
Ferritin
True or False:
Since ferratin has ferroxidase activity, it can convert Fe3+ to Fe2+
True
What three structures are important for iron export?
-Ferroportin
-Hephaestin
-Transferrin
What is the function of Hephaestin—a structure that is important for iron export?
Hephaestin: oxidizes Fe2+ to Fe3+
What is the function of Transferrin—a structure that is important for iron export?
Transferring binds and transports Fe3+ in the serum
Iron export takes places from what 3 structures?
1) Enterocytes
2) Hepatocytes
3) RE macrophages
How does iron import occur?
1) Transferrin bound to Fe3+ bind to the transferrin receptor (endocytosis)
2) Endosome will increase pH
3) Iron liberated from transferrin
4) Free iron leaves endosome via DMT1
5) Ferritin (storage)
What are the two main proteins that control iron transport?
1) Hepcidin: Negative regulator of iron transport
2) Erythroferrone: Positive regulator of iron transport
How does Hepcidin act as a negative regulator of iron transport?
When present, it binds to ferroportin and triggers its internalization. If ferroportin gets internalized, iron cannot be exported.
How does Erythroferrone act as a postive regulator of iron transport?
Represses the expression of hepcidin
If someone has an infection, positive acute phase reactants such as ____ increase, leading to ____ ____. Taken together, this is known as _____
hepcidin
iron witholding
nutritional immunity
True or False:
Reducing iron availability can slow down an infection
True
How are hepcidin and serum iron levels affected during nutrional immunity?
Hepcidin: increases
Serum iron: decreases
Bacterial Growth: decreases
Under low iron conditions, iron regulatory proteins (IRP’s) bind to ____, which result in the production of the ____ receptor
3’ iron responsive elements (IRE); transferrin receptor (allow for greater transport of iron)
What happens to the iron regulatory protein (IRP) and the iron-responsive-element under high level iron conditions?
IRP do not bind to IRE. Therefore, there is less translation of transferrin receptor.
The ___ ___ ___ is the RNA sequence found in the non-coding part of the transferrin mRNA
Iron Response Element
___ is a condition caused by low hemoglobin. Symptoms include: extreme fatigue and dizziness.
Anemia
______ is the type of anemia that is characteristic of an iron deficiency. In this disorder, circulating RBCs are smaller than the usual size of RBCs and have decreased red color
Microcytic hypochromic anemia
What would you expect to see on CBC if one has anemia? (Hb, hematocrit?)
Low hemoglobin/hematocrit
Also: microcytic hypochromic anemia
What populations may develop anemia?
1) Vegetarians
2) Pregnant women
3) Blood loss
4) Poor absorption conditions
What vitamins can prevent anemia?
-Iron
-Vit C
-Folate
-B12
You can develop anemia of chronic disease under what conditions?
If you have untreated chronic ____or ____; increased expression of ____, nutritional immunity, or iron witholding
inflammation; infection; hepcidin
Anemia of chronic disease look similar to what type of anemia?
Microcytic hypochromic anemia
Macrocytic Normochromiac Anemia is a result of deficiency in vitamin ____or ___
B12 ; folate
True or False: Hereditary hemochromatosis is a condition in which minimal amounts of iron are made
False - excessive amounts of iron are made
What is the cause of hereditary hemochromatosis? Treatment?
Mutations in hepcidin, ferroportin, and regulators of hepcidin
Treatment: phlebotomy
Iron overload can occur by taking supplements. How can iron poisoning be treated?
Chelating agents
What are the three positive acute phase reactants?
1) Ferritin
2) C Reactive Protein
3) Hepcidin
(Serum levels of these will elevate upon infection or inflammation)
____ is the only iron (Fe2+) exporter
Ferroportin
Where does iron import take place from?
1) Erythroid cells
2) Hepatocytes
What three structures are important for iron import?
1) Transferrin: Binds and transports Fe3+
2) Transferrin Receptor: Binds Tf-Fe3+ and internalizes it
3) Divalent Metal Transporter: Exports Fe3+ out of endosome
What three structures are important for iron import?
1) Transferrin: Binds and transports Fe3+
2) Transferrin Receptor: Binds Tf-Fe3+ and internalizes it
3) Divalent Metal Transporter: Exports Fe3+ out of endosome
What are the three negative acute phase reactants?
1) Albumin
2) Pre-albumin
What are the three negative acute phase reactants?
1) Albumin
2) Pre-albumin
3) Tranferrin
serum levels of these analytes decrease upon infection/inflammation
________ are proteins that bind to the transferrin receptor mRNA and stabilize it to promote its translation/iron transport. They are inactivated by high iron levels.
Iron regulatory proteins
What four structures are important for iron import?
1) Transferrin
2) Transferrin Receptor
3) Divalent metal transporter
4) Ferritin
What does a CBC evaluate?
Hemoglobin
Hematocrit
RBC/WBC
Platlets
What three markers could you use to assess iron status? Which would you prefer to use if person is feeling ill/has other infection/inflammatory conditions?
Ferritin, Transferrin, or Transferrin Receptor
What value will elevate as anemia worsens?
Total iron binding capacity
