43 Iron Metabolism Flashcards
Iron components in the average Person (mg/ % of total body iron)
Hemoglobin
Storage iron (ferritin , hemosidirin)
Myoglobin
Labile pool
Other tissue iron
Transport iron
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%)
Hemoglobin, which is _____% iron by weight, contains approximately____ g of body iron in men and ____ g in women.
0.34%
2 g in men
1.5 g in women
One milliliter of packed erythrocytes contains approximately ____ mg of iron.
1 mg of iron
Storage forms of iron
Ferritin and hemosiderin
Water-soluble or Water-insoluble
Ferritin
Hemosiderin
Ferritin: Water-soluble
Hemosiderin: Water-insoluble
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
H (heavy)
Much of the storage iron in the liver and spleen is in ferritin containing mostly______ subunits.
L subunits
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.
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.
The cargo protein_____, a ferritin receptor, is increased during iron deficiency and delivers ferritin to lysosomes.
NCOA4
Found predominantly in macrophages
Microscopically, in unstained tissue sections or marrow films, it appears as clumps or granules of golden refractile pigment.
Hemosiderin
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
Myoglobin
Size of the labile iron pool
80–90 mg of iron
It is now sometimes considered to be equivalent to the chelatable iron pool.
Labile iron pool
Includes cytochromes and other iron-containing enzymes
Although a small compartment, it is vital and sensitive to iron deficiency.
Tissue iron
Amount of tissue iron
6–8 mg
The smallest but the most active of the iron compartments
Transport iron
Its iron, almost entirely carried by transferrin, normally turns over at least 10 times each day.
Amount of transport iron
3 mg
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+
Transferrin
Normally, approximately ______of the transferrin iron-binding sites are occupied by iron.
One-third
Apotransferrin (transferrin devoid of iron) is synthesized by
Hepatocytes and cells of the monocyte macrophage system
RDA for Iron
Male 19 and above
Female 19 - 50 years
Female 51 years and above
Pregnant
Lactation
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
Amount of iron excreted in stool
~1 mg/day
Increase or decrease iron absorption
Oxalates, phytates, and phosphates
Hydroquinone, ascorbate, lactate, pyruvate, succinate, fructose, cysteine, and sorbitol:
Oxalates, phytates, and phosphates; red wine: decrease iron absorption
Hydroquinone, ascorbate, lactate, pyruvate, succinate, fructose, cysteine, and sorbitol: increase iron absorption
Iron normally enters the body through the gastrointestinal tract, mostly through the
Enterocytes of the duodenum
The reduction of ferric iron to ferrous iron, in part by duodenal _____________________, ferrous iron is transported into the intestinal villus cell by the _________________.
Cytochrome b (Dcytb) reductase
Divalent metal transporter (DMT)-1
Basolateral export of ferrous iron is mediated by _________ in association with hephaestin and plasma ceruloplasmin to oxidize iron to the ferric state.
Ferroportin
Ferric iron is taken up by plasma_______________.
Apotransferrin
Destruction of aged erythrocytes and hemoglobin degradation occur within
Macrophages
In humans, the destruction and production of erythrocytes generates most of the iron flux in and out of plasma
Monocyte–Macrophage System
(20–25 mg/day recycled in adults vs 1–2 mg/day absorbed)
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.
80%
Thus, 20% to 70% percent of the hemoglobin iron of nonviable erythrocytes reappears in circulating red cells in _____ days.
12 days
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.
Hepcidin
Hepcidin is produced predominantly by
Hepatocytes
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.
Defensins
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
TRUE
Patients with iron overload and high plasma iron levels are susceptible to such infections, such as with Vibrio vulnificus and Yersinia enterocolitica
Hepcidin exerts its iron-regulatory effect by binding to_________, a transmembrane iron-export protein expressed on enterocytes, macrophages, and hepatocytes.
Ferroportin
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
(IL)-6
Hepcidin transcription is regulated in an iron-dependent manner by the ___________ pathway.
BMP pathway
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
Hemojuvelin
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
Tmprss6 (also called matriptase 2)
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.
Iron-refractory iron-deficiency anemia
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.
Erythroferrone
Erythroferrone binds BMP2/6 secreted by sinusoidal endothelial cells in the space of Disse and thereby inhibits BMP signaling and hepcidin transcription in hepatocytes
TRUE OR FALSE
Within hours after the onset of systemic infection, plasma iron concentration increases.
FALSE
Within hours after the onset of systemic infection, plasma iron concentration decreases.
The main human cytokine responsible for hepcidin induction
IL-6
Plays a role in the binding and endocytosis of diferric transferrin
A major mechanism for regulation of iron metabolism
TfR1
Synthesis of TfR1 is induced by iron deficiency.
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.
TfR2
The final steps of heme synthesis take place in____________, where iron is inserted into protoporphyrin by the enzyme__________________.
Mitochondria
Ferrochelatase
Ringed sideroblast can be stained by
Prussian blue
TRUE OR FALSE
In iron deficiency and in the anemia that accompanies chronic disorders, sideroblasts almost disappear from the marrow
TRUE
In iron deficiency and in the anemia that accompanies chronic disorders, sideroblasts almost disappear from the marrow
In normal, iron-replete marrow, much smaller siderotic granules are also demonstrable, scattered in the cytoplasm of about___________of erythroblasts
One-third
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)
Most iron loss occurs by way of
Desquamated intestinal cells in the feces : 1 mg per day
Exfoliation of skin and dermal appendages and perspiration result in much smaller losses.
Total daily iron loss
Males:
Menstruating women:
Total daily iron loss for
Males: 1 mg
Menstruating women: 2mg
