43 Iron Metabolism

Question 1

Iron components in the average Person (mg/ % of total body iron)

Hemoglobin
Storage iron (ferritin , hemosidirin)
Myoglobin
Labile pool
Other tissue iron
Transport iron

Answer 1

Iron components in the average Person (mg/ % of total body iron)

Hemoglobin: 2000 (67%)
Storage iron (ferritin , hemosidirin): 1000 (27%)
Myoglobin: 130 (3.5%)
Labile pool: 80 (2.2%)
Other tissue iron: 8 (0.2%)
Transport iron: 3 (0.08%)

Question 2

Hemoglobin, which is _____% iron by weight, contains approximately____ g of body iron in men and ____ g in women.

Answer 2

0.34%
2 g in men
1.5 g in women

Question 3

One milliliter of packed erythrocytes contains approximately ____ mg of iron.

Answer 3

1 mg of iron

Question 4

Storage forms of iron

Answer 4

Ferritin and hemosiderin

Question 5

Water-soluble or Water-insoluble

Ferritin
Hemosiderin

Answer 5

Ferritin: Water-soluble
Hemosiderin: Water-insoluble

Question 6

Subunit of ferritin that have ferroxidase activity, thereby enabling ferritin to take up or release iron quite rapidly.

Takes up iron more readily but retains it less avidly

Answer 6

H (heavy)

Question 7

Much of the storage iron in the liver and spleen is in ferritin containing mostly______ subunits.

Answer 7

L subunits

Question 8

TRUE OR FALSE

Except under conditions of inflammation, the plasma (serum) ferritin concentration usually correlates with total-body iron stores, making measurement of serum ferritin levels important in the diagnosis of disorders of iron metabolism.

Answer 8

TRUE

Except under conditions of inflammation, the plasma (serum) ferritin concentration usually correlates with total-body iron stores, making measurement of serum ferritin levels important in the diagnosis of disorders of iron metabolism.

Question 9

The cargo protein_____, a ferritin receptor, is increased during iron deficiency and delivers ferritin to lysosomes.

Answer 9

NCOA4

Question 10

Found predominantly in macrophages

Microscopically, in unstained tissue sections or marrow films, it appears as clumps or granules of golden refractile pigment.

Answer 10

Hemosiderin

Question 11

Structurally similar to hemoglobin, but it is monomeric rather than tetrameric

It is present in small amounts in all skeletal and cardiac muscle cells where it may serve as an oxygen reservoir

Answer 11

Myoglobin

Question 12

Size of the labile iron pool

Answer 12

80–90 mg of iron

Question 13

It is now sometimes considered to be equivalent to the chelatable iron pool.

Answer 13

Labile iron pool

Question 14

Includes cytochromes and other iron-containing enzymes

Although a small compartment, it is vital and sensitive to iron deficiency.

Answer 14

Tissue iron

Question 15

Amount of tissue iron

Answer 15

6–8 mg

Question 16

The smallest but the most active of the iron compartments

Answer 16

Transport iron

Its iron, almost entirely carried by transferrin, normally turns over at least 10 times each day.

Question 17

Amount of transport iron

Answer 17

3 mg

Question 18

A dumbbell-shaped glycoprotein with a molecular weight of approximately 80 kDa where each of the two globular domains contains a binding cleft for Fe3+

Answer 18

Transferrin

Question 19

Normally, approximately ______of the transferrin iron-binding sites are occupied by iron.

Answer 19

One-third

Question 20

Apotransferrin (transferrin devoid of iron) is synthesized by

Answer 20

Hepatocytes and cells of the monocyte macrophage system

Question 21

RDA for Iron

Male 19 and above
Female 19 - 50 years
Female 51 years and above
Pregnant
Lactation

Answer 21

RDA for Iron

Male 19 and above: 8 mg
Female 19 and above: 18 mg
Female 51 years and above: 8 mg
Pregnant: 27 mg
Lactation: 9 mg

Question 22

Amount of iron excreted in stool

Answer 22

~1 mg/day

Question 23

Increase or decrease iron absorption

Oxalates, phytates, and phosphates

Hydroquinone, ascorbate, lactate, pyruvate, succinate, fructose, cysteine, and sorbitol:

Answer 23

Oxalates, phytates, and phosphates; red wine: decrease iron absorption

Hydroquinone, ascorbate, lactate, pyruvate, succinate, fructose, cysteine, and sorbitol: increase iron absorption

Question 24

Iron normally enters the body through the gastrointestinal tract, mostly through the

Answer 24

Enterocytes of the duodenum

Question 25

The reduction of ferric iron to ferrous iron, in part by duodenal _____________________, ferrous iron is transported into the intestinal villus cell by the _________________.

Answer 25

Cytochrome b (Dcytb) reductase Divalent metal transporter (DMT)-1

Question 26

Basolateral **export of ferrous iron** is mediated by _________ in association with **hephaestin** and plasma **ceruloplasmin** to oxidize iron to the ferric state.

Answer 26

Ferroportin

Question 27

Ferric iron is taken up by plasma_______________.

Answer 27

Apotransferrin

Question 28

Destruction of aged erythrocytes and hemoglobin degradation occur within

Answer 28

Macrophages

Question 29

In humans, the destruction and production of erythrocytes generates **most of the iron flux in and out of plasma**

Answer 29

Monocyte–Macrophage System (**20–25 mg/day** recycled in adults vs 1–2 mg/day absorbed)

Question 30

This proceeds at a rate sufficient to release approximately **20%** of the hemoglobin iron from the cell to the plasma compartment within a few hours Approximately _____% of this iron is rapidly reincorporated into hemoglobin.

Answer 30

80%

Question 31

Thus, **20% to 70%** percent of the hemoglobin iron of nonviable erythrocytes reappears in circulating red cells in _____ days.

Answer 31

12 days

Question 32

Regulates plasma iron concentrations by controlling the **absorption of iron by the intestinal epithelial enterocytes** and its **release from iron-recycling macrophages and hepatocytes** involved in iron storage.

Answer 32

Hepcidin

Question 33

**Hepcidin** is produced predominantly by

Answer 33

Hepatocytes

Question 34

The structural similarity of hepcidin and a class of antimicrobial peptides termed________ suggests that the hormone evolved from the latter to modulate iron homeostasis as a mechanism of body **defense against microorganisms.**

Answer 34

Defensins

Question 35

# TRUE OR FALSE Patients with iron overload and high plasma iron levels are susceptible to such infections, such as with Vibrio vulnificus and Yersinia enterocolitica

Answer 35

TRUE Patients with iron overload and high plasma iron levels are susceptible to such infections, such as with **Vibrio vulnificus** and **Yersinia enterocolitica**

Question 36

Hepcidin exerts its iron-regulatory effect by binding to_________, a transmembrane iron-export protein expressed on enterocytes, macrophages, and hepatocytes.

Answer 36

Ferroportin

Question 37

Hepcidin production is stimulated by inflammatory cytokines such as interleukin ____, and the **overproduction of hepcidin** is an important factor in the pathogenesis of the **anemia of chronic inflammation**

Answer 37

(IL)-6

Question 38

Hepcidin transcription is regulated in an iron-dependent manner by the ___________ pathway.

Answer 38

BMP pathway

Question 39

Acts as an **inhibitor of the interaction of BMP with the receptor** Autosomal recessive mutations cause a **very severe form of hereditary hemochromatosis**, serves as a coreceptor for the BMPs

Answer 39

Hemojuvelin

Question 40

A membrane serine protease that likely acts by **proteolysis of hemojuvelin** and perhaps also other proteins in the BMP receptor complex **Inhibitory effect of hepcidin transcription**

Answer 40

Tmprss6 (also called matriptase 2)

Question 41

Humans with mutations of the Tmprss6 ortholog were shown to manifest this condition IDA that does not improve with oral iron therapy and responds only partially to parenteral iron therapy.

Answer 41

Iron-refractory iron-deficiency anemia

Question 42

An **erythropoietin-induced erythroblast-secreted glycoprotein** that acts on hepatocytes to **suppress their hepcidin production** and is required for rapid suppression of hepcidin after hemorrhage or erythropoietin administration.

Answer 42

Erythroferrone ## Footnote Erythroferrone binds BMP2/6 secreted by sinusoidal endothelial cells in the space of Disse and thereby inhibits BMP signaling and hepcidin transcription in hepatocytes

Question 43

# TRUE OR FALSE Within hours after the onset of systemic infection, plasma iron concentration increases.

Answer 43

FALSE **Within hours** after the onset of systemic **infection**, plasma iron concentration **decreases**.

Question 44

The main human cytokine responsible for **hepcidin induction**

Answer 44

IL-6

Question 45

Plays a role in the **binding and endocytosis of diferric transferrin** **A major mechanism for regulation of iron metabolism**

Answer 45

TfR1 ## Footnote **Synthesis of TfR1 is induced by iron deficiency.**

Question 46

Also endocytic for holotransferrin, is not thought to be involved in delivering iron to cells but its **hepatic** expression is necessary for normal **hepcidin expression and regulation**.

Answer 46

TfR2

Question 47

The final steps of heme synthesis take place in____________, where iron is inserted into protoporphyrin by the enzyme__________________.

Answer 47

Mitochondria Ferrochelatase

Question 48

Ringed sideroblast can be stained by

Answer 48

Prussian blue

Question 49

# TRUE OR FALSE In iron deficiency and in the anemia that accompanies chronic disorders, sideroblasts almost disappear from the marrow

Answer 49

TRUE In iron deficiency and in the anemia that accompanies chronic disorders, sideroblasts almost disappear from the marrow

Question 50

In normal, iron-replete marrow, much smaller siderotic granules are also demonstrable, scattered in the cytoplasm of about___________of erythroblasts

Answer 50

One-third ## Footnote When heme synthesis is impaired, as in **lead poisoning or in the sideroblastic anemias**, the mitochondria accumulate excessive amounts of amorphous iron aggregates Seen by light microscopy as a ring of large blue siderotic granules encircling the erythroblast nucleus **(ringed sideroblast)**

Question 51

Most iron loss occurs by way of

Answer 51

Desquamated intestinal cells in the **feces** : **1 mg per day** ## Footnote Exfoliation of skin and dermal appendages and perspiration result in much smaller losses.

Question 52

Total daily iron loss Males: Menstruating women:

Answer 52

Total daily iron loss for Males: **1 mg** Menstruating women: **2mg**