Iron Metabolism & Absorbtion

Question 1

What is Fe used for?

Answer 1

Readily exchanges e⁻, ideal catalyst for redox rxns, important role in e⁻ transport chain, O₂ transport, heme, stored in ferritin, myoglobin & enzymes

Question 2

Where is Fe stored?

Answer 2

Much in RBCs some stored in ferritin, myoglobin & enzymes

Question 3

What regulates bodies Fe content?

Answer 3

Modulating absorption (intestine)

Question 4

What is the regulated pathway for Fe excretion?

Answer 4

There isn’t one

Question 5

What does too much Fe do?

Answer 5

It’s interaction w/ O₂ can promote cellular damage

Question 6

What is the total amount of Fe found in the body and how much is in RBCs?

Answer 6

3-5 g total, 2.7 g in RBCs

Question 7

How much Fe is needed daily to support Hb production?

Answer 7

25 mg

Question 8

What is the distribution of Fe in a normal man?

Answer 8

Hemoglobin: 67%
Storage Fe: 27%
Myoglobin: 5%
Fe-requiring proteins: 1%

Question 9

In what forms does Fe exist?

Answer 9

Fe2+ (ferrous) Fe3+ (ferric)

Question 10

In what forms does Fe exist?

Answer 10

Fe²⁺ (ferrous) Fe³⁺ (ferric)

Question 11

What is ferritin, its location, and purpose?

Answer 11

Intracellular protein found in most cells that binds thousands of Fe3+/molecule

Question 12

What is ferritin, its location, and purpose?

Answer 12

Intracellular protein found in most cells that binds thousands of Fe³⁺/molecule

Question 13

Where is excess Fe mainly stored?

Answer 13

Liver, lunges, pancreas

Question 14

What are the Fe transport proteins?

Answer 14

Ferrireductase, DMT1 (divalent transporter-1), Hephaestin, Ferroportin

Question 15

In what form is dietary Fe?

Answer 15

Fe³⁺ (ferric)

Question 16

What reduces ferric Fe to the ferrous form?

Answer 16

Dcytb (duodenal cytochrome-like b, Fe³⁺→Fe²⁺, ferric→ferrous

Question 17

What reduces ferric Fe to the ferrous form?

Answer 17

Dcytb (duodenal cytochrome-like b, Fe³⁺→Fe²⁺, ferric→ferrous

Question 18

What transports Fe outside the cell into the blood?

Answer 18

Ferroportin, basolateral surface → blood

Question 19

What does ferroportin require to perform transport?

Answer 19

Ferroxidase (Hephaestin)

Question 20

What carries Fe from the blood to the bone marrow?

Answer 20

Transferrin

Question 21

What must first happen for Fe to be transported by transferrin into the bone marrow?

Answer 21

Fe must be changed from ferrous to ferric, Fe³⁺→Fe²⁺

Question 22

What must first happen for Fe to be transported by transferrin into the bone marrow?

Answer 22

Fe must be changed from ferrous to ferric, Fe³⁺→Fe²⁺

Question 23

What does transferrin do?

Answer 23

Binds 1-2 Fe³⁺/molecule w/ high affinity and carries Fe blood → tissues in a non-toxic form

Question 24

What size and what type of protein is transferrin?

Answer 24

76 kDa serum glycoprotein

Question 25

Describe tranferrin-receptor mediated endocytosis?

Answer 25

Transferrin binds Fe³⁺→ transferrin binds transferrin-R (TfR)→ endocytosed into endosome w/ clathrin coat→ clathrin coat removed→ proton pump ↓ pH to 5.5→ Fe released→ endosome fusses with cell exterior→ pH ↑ to 7.4→ TfR releases transferrin

Question 26

What is the "kiss & run" hypothesis?

Answer 26

The idea that the TfR mediated transfer of Fe to the MT is so efficient that the endosome briefly docks "kisses" the MT transfers Fe directly & leaves "runs", No cytoplasmic transport protein needed

Question 27

What is the function of Steap3 ferroreductase?

Answer 27

Reduces Fe³⁺→Fe²⁺ in the endosome

Question 28

What is the function of DMT1?

Answer 28

Transports Fe²⁺ out of endosome

Question 29

What are causes of Fe deficiency?

Answer 29

Insufficient dietary Fe, menstration, Aspirin abuse

Question 30

What are symptoms of Fe deficiency?

Answer 30

Gi tract ulcers, hypochromic microcytic anemia

Question 31

What is the treatment for Fe deficiency?

Answer 31

Dietary Fe supplement

Question 32

What are causes of Fe overloading?

Answer 32

Hereditary hemochromatosis, repeated blood transfusions (conditional Fe overloading)

Question 33

What is the clinical definition of hereditary hemochromatosis?

Answer 33

Organ dysfuntion due to Fe orverload

Question 34

What is the genetic definition of hereditary hemochromatosis?

Answer 34

Autosomal recessive mutation in HFE gene

Question 35

What is the functional definition of hereditary hemochromatosis?

Answer 35

Malregulation of Fe uptake & export by entreocyte

Question 36

What is the clinical presentation of hereditary hemochromatosis?

Answer 36

Elevated total body Fe w/ cell injury, liver damage, diabetes, heart failure, >400ng/mL, visible Fe overloading in liver

Question 37

What is the function of the HFE protein and where is it found?

Answer 37

Binds transferrin-R

Question 38

What is the role of HFE in hereditary hemochromatosis?

Answer 38

Mutation of HFE causes hereditary hemochromatosis

Question 39

What is the treatment for hereditary hemochromatosis?

Answer 39

blood letting 1 unit blood/week up to 80 weeks → 1 unit/every other month, ExJade

Question 40

What does ExJade do and what are its side effects?

Answer 40

Fe chelator, can cause nephrotic syndrome & death

Question 41

What is the role of Hfe in signal transduction?

Answer 41

It is bound to Tfr1 until Fe competitively outbinds it → Hfe binds Tfr2 → induces hepcidin expression

Question 42

What the relationship b/t Fe levels and hepcidin expression?

Answer 42

Fe replete= ↑ hepcidin | Fe deplete= ↓ hepcidin

Question 43

What is the role of Hfe in signal transduction?

Answer 43

It is bound to Tfr1 until Fe competitively outbinds it → Hfe binds Tfr2 → ↑ hepcidin expression

Question 44

Describe the role of bone morphogenic protein in hepcidin signaling?

Answer 44

↑Fe= ↑BMP6, BMP binds BMPR→R-SMAD binds SMAD4→ SMAD complex binds hepcidin promoter→ ↑ hepcidin

Question 45

What is juvenile hemochromatosis?

Answer 45

Fe overloading disease that manifests in the 2nd decade of life

Question 46

What is the role of hemojuvelin (HJV) in juvenile hemochromatosis?

Answer 46

↓HJV→ ↓BMPR effectiveness, Hemojuvelin is co-receptor for BMPR that enhances BMPR activity

Question 47

What is the role of hepcidin antimicrobial peptide (HAMP) gene in juvenile hemochromatosis?

Answer 47

↓HAMP→ ↓hepcidin, HAMP makes hepcidin, rare condition

Question 48

What is the cause of non-hereditary hemochromatosis?

Answer 48

Blood transfusions

Question 49

What is the treatment for non-hereditary hemochromatosis?

Answer 49

ExJade

Question 50

What does the transmembrane serine-protease (TMPRSS6) do and where is it made?

Answer 50

↑TMPRSS6→ ↓HJV, made in the liver