Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MCT > Iron Hemostasis > Flashcards

Iron Hemostasis Flashcards

1
Q

Most abundant metal in body

A

Iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Consequences of too little iron

A

Insufficient for essential proteins (hemoglobin, ribonucleotide reductase, OxPhos complexes, catalase, peroxidase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Consequences to too much iron

A

Accumulates in tissues (oxygen free radicals, lipid peroxidiation, DNA damage, tissue fibrosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Carries iron throughout circulation
Binds 2 iron atoms per molecule
Abundant

A

Transferrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Stores iron oxides within cells (up to 4500 iron atoms)

Can mobilize iron when needed

A

Ferritin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

___________ bound iron is the major source of iron for production of RBCs

A

Transferrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

__________ break down RBCs after 120 days, free the iron and return it to transferrin in circulation

A

Macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Only source of iron

A

Diet
(absorbed in intestines)
Extra iron stored in liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cell types that must but import and export iron

A

Intestinal epithelial cells (duodenum)

Hepatocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cell type that just need to import (not export) iron

A

RBCs (in bone marrow)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cell type that needs to export iron (taken in by phagocytosis of RBCs)

A

Macrophages in liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Only normal way to excrete iron from the body

A

Sloughing of intestinal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Function of ferric reductase enzymes

A

Reduce dietary Fe3+ to Fe2+ for absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Transports Fe2+ across apical membrane into enterocyte

Moved by proton influx (H+ provided by acid efflux from stomach) - only functions in low pH

A

Divalent metal transporter 1 (DMT1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Some of the iron that enters the enterocyte is stored as _________ - that iron is lost from the body when enterocytes are sloughed

A

Ferritin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Some iron passes through the enterocyte, leaving through a distinct basolateral transporter, __________

A

Ferroportin (Fpn)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Iron released from the cell by ferroportin must be _________ by a ferroxidase enzyme to be loaded onto serum transferrin

A

Oxidized to Fe3+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Heme with iron can also be transported through a distinct heme transporter through the apical membrane of an enterocyte
Once inside, iron is liberated from heme by _______________

A

Heme oxygenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do macrophages import and export iron?

A

Phagocytosis of RBS brings it in, export through ferroportin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Steps for iron uptake through the transferrin cycle in erythroid cells

A

Tfr1 (transferrin receptor) - clathrin-mediated endocytosis
Acidic environment frees iron
Reduced to Fe2+
DMT1 importer from the endosomal membrane (H+ allows for cotransport)
(DMT1 has differences in C-terminus that determine membrane localization)

21
Q

Only known transmembrane importer for non-heme iron (in mammals)

A

DMT1

22
Q

Only known cellular iron exporter (in mammals)

A

Ferroportin

23
Q

RNA stem-loop structures found in non-coding portions (5’ and 3’ untranslated regions) of some mRNAs encoding proteins involved in iron homeostasis

A

Iron regulatory elements (IREs)

24
Q

The role of an IRE depends on:

A

Where it is located in the mRNA

25
Q

________ bind to IREs to prevent other proteins from acting on the mRNAs

A

Iron regulatory proteins (IRPs)

26
Q

Both IRP1 and IRP2 are in their active, RNA-binding forms when cellular iron content is ______

A

Low

27
Q

When cellular iron content increases, an iron sulfur cluster (4Fe-4S) forms and is incorporated into _________, converting it from an RNA binding protein to an enzyme, cytoplasmic aconitase (a similar aconitase is part of the TCA cycle in mitochondria)

A

IRP1

28
Q

When cellular iron content increases, iron and/or heme binds to ______, signaling for its ubiquination and subsequent degradation

A

IRP2

29
Q

IRPs binding to IREs at the _______ ends of mRNAs (i.e., preceding the sequence that codes for protein) prevent ribosomal initiation complexes from forming on the mRNA, thus blocking translation
** low iron condition

A

5’

30
Q

IRPs binding to IREs at the _____ ends of mRNAs (I.e., following the sequence that codes for protein) protect the mRNA from endonucleases (enzymes that break RNA into small pieces), thus enhancing translation
** low iron condition

A

3’

31
Q

When cellular iron content is _________ IRPs cannot bind to IREs
• Bare IREs at the 5’ ends of mRNAs do not block translation
• Bare IREs at the 3’ ends of mRNAs do not block endonucleases; endonucleases recognize sensitive sites nearby in the mRNA and degrade it

A

High

32
Q

5’ IREs regulate expression of ferritin, ferroportin, aminolevulinic acid synthase (heme biosynthesis)
• IRE/IRP regulation allows iron-deficient cells to turn ________ production of ferritin (the iron storage protein)

A

Off

33
Q

3’ IREs regulate expression of transferrin receptor and DMT1
• IRE/IRP regulation allows iron-deficient cells to turn ____ production of transferrin receptor

A

On

(for more iron uptake)

34
Q

Master regulator of iron balance

A

Hepcidin

35
Q

Circulating defense-like hormone produced by the liver (weak anti-microbial activity)
Short-lived, cleared by kidneys (detectable in urine)

A

Hepcidin

36
Q

Causes endocytosis and degradation of ferroportin so iron can’t be exported

A

Hepcidin

37
Q

How is hepcidin expression modulated by iron status

A

More iron triggers more hepcidin, to limit iron absorption

Low iron, reduces hepcidin to increase iron absorption

38
Q

Prevalent genetic disorder
Chronic slight increase in dietary iron absorption
Increased serum iron
Iron deposits in heart, liver, endocrine tissues

A

Hemochromatosis

genetic iron overload

39
Q

Common cause of hemochromatosis

A

Hepcidin deficiency

(unregulated ferroportin activity leads to increased serum iron and tissue iron deposition in lever, heart, endocrine tissues)
Increased intestinal iron absorption

40
Q

Mutations in hepicdin gene (no functional protein)
Mutations in ferroportin (no longer regulated by hepcidin)
Mutations in HFE, TFR2, HJV (liver membrane proteins that signal to induce hepcidin expression)
These could all cause:

A

Hemochromatosis

41
Q

Hemochromatosis gene
Specific ligand to induce hepcidin expression through a BMP/SMAD signaling pathway
Circulating protein - binds receptor to trigger hepcidin expression

A

Bone morphogenetic protein 6 (BMP6)

42
Q

Hemochromatosis gene

Co-receptor for BMP6 to stimulate hepcidin expression through SMAD signaling

A

HJV (hemojuvelin)

43
Q

Hemochromatosis genes

Interact with each other and induce hepcidin

A

HFE and TFR2 (transferring receptor 2)

44
Q

Inherited iron deficiency anemia
Failure to respond to iron treatment
Elevated hepcidin levels (opposite of hemochromatosis)

A

IRIDA (Familial iron-refractory, iron deficiency anemia)

45
Q

Common causes of iron deficiency anemia

A

Inadequate iron availability
Increased iron loss

(corrects rapidly with effective iron treatment)

46
Q

Iron deficiency
Decreased hepcidin
What effect on ferroportin?

A

Increased ferroportin

47
Q

IRIDA
Increased hepcidin
What effect?

A

Interruption of intestinal absorption

Macrophage iron retention (prevents secretion)

48
Q

IRIDA families have mutations in a serine protease _______ that interfere with protease activity

A

TMPRSS6

(normally cleaves HJV - inhibits SMAD pathway and hepcidin tc)
mutation prevents cleavage and leads to increased hepcidin

MCT (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions