Brainscape's Knowledge GenomeTM

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


See full index

Chronic Disease > Fe Metabolism And Diseasw > Flashcards

Fe Metabolism And Diseasw Flashcards

1
Q

Why is fe stored / deposited

A

Can’t be excreted

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

Which state does fe need to be in for acquisition into cell

A

Fe2/ soluble ferrous form

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

Why is fe toxic

A

Fenton chemistry

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

What enzymes convert it into redox states

A

Fe2 to fe3 by cu containing oxidases for transport
Fe3 to fe2 by reductases

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

Which 2 ways is fe from diet

A

As ferritin - caged fe3 ion

Heme (from meat)- in protoporphyrin ring

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

Why is fe needed more in cell than cu and give examples

A

Mroe enzymes

Cox haem
Ferrochelatase
Helicases
Enzymes for nucleotide synthesis
Translation

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

Same amount of fe taken in by gut is removed from body everyday. How

A

Removal Dead skin cells/ mucous

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

Where does fe go for storage

A

Liver

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

Why would fe go to bone marrow

A

For heme synthesis and rbc incorporation

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

Which reductase for fe3 to fe2 in enterocytes lumen side

A

Dcytb

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

What does this allow fe2 to bind

A

Dmt1 (duodenal importer)

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

Heme can also be imported into enterocytes from diet. How

A

Hcp1 transporter and fe is released by Heme oxidase 1 HO1

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

What can fe then do if in excess enterocytes

A

Either enter ferritin or get oxidised back to fe3 via cu containing oxidases back onto ferroportin exporter

Then binds transferrin

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

What is the fe oxidase called in enterocytes vs mitochondria

A

Hephaestrin

Ceruloplasmin in mt

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

What is fe from the fe-Tf complex endocytosed from blood into and which receptor

A

Tfr1 receptors into clathrin coated endosomes

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

What happens in the endosome

A

Ph change to 5.5 via proton pump mediated by steap3 fe reductase , releasing fe

Fe reduced to fe2 transported out of endosome by dmt1 and incorporated into enzymes

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

What happens to ferroportin after

A

Recycled back up

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

Which types of cells need this tfr1 uptake for fe

A

Erythroid cells

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

Which enzyme do macrophages have to breakdown heme

A

HO1

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

What proteins allow it to endocytose free heme or hb

A

Hemopexin and haptoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Which cu containing oxidase does mt have and what exporter

A

Ceruloppasmin

Also has a ferroportin

Then binds transferrin in vlood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which protein needed for mrna / translational level regulation of fe metabolism

A

Irp1

23
Q

What does dissassembly of fe-s in low fe cause for irp1

A

It’s change from aconitase enzyme to irp1 and conformational change to open conformation = binds ires on mrna

24
Q

What does irp1 binding in low fe at 5’ end cause

A

Block of translation in low fe of genes like aconitase, ferritin storage, heme synthesis , fe efflux ferroportin

25
Q

What does binding to 3’ end do only in low fe

A

Protects transcripts for tfr1 and dmt1 for import

26
Q

Why is irp2 different to irp1 when fe is high

A

Irp1 just changed to close confirmation whereas irp2 is degraded by fbx15 e3 ligase complez

27
Q

What are ires

A

A-helices which have a c bulge/loop

28
Q

Which event causes fe-s dissassembly even when fe can be high, causing irp1 binding even if fe is already high in cells

A

Oxidative stress

29
Q

What backup system degrades it because of this

A

Fbx15 e3 ligase complex

30
Q

Which tf is used for txn level regulation

A

Hif2a

31
Q

What happens when fe is low or hypoxia occurs

A

Hif2a translocates to nucleus and activates txn of genes like dmt1, reductases like dcytb

32
Q

What happens to Hif2a in normoxia or high fe levels

A

Targeted for degradation by ubiquitination which needs hif to be hydroxylated first by phd1-3

33
Q

Why does phd1-3 only work to hydroxylate hif when fe is high

A

They are fe containing proteins

34
Q

During high fe levels mainly in blood, what happens to regulate ferroportin export of fe in eg liver, enterocytes and macrophages

A

Hepcidin

35
Q

What does fe bound transferrin bind in high fe levels

A

Tfr2 instead of tfr1

36
Q

What else recruited to tfr2 in high fe which altogether with transferrin-fe and tfr2 causes erk1/2 signalling and helcidin txn

A

Hfe- hemachormatoais protein

37
Q

What does hfe bind to in low fe and be sequestered = no erk signalling

A

Tfr1

38
Q

Why would hepcidin be reduced in exp during fe deficiency

A

Ferroportin needed and hepcidin usually binds ferroportin and internalises and degradation occurs

39
Q

Explain the other pathway of hepcidin activation

A

Bmp6 increases when fe increases

Binds hjv bmpr receptor complex

Causes smad 1,5,8 phos

Recruits smad 4

Activates txn of hepcidin

40
Q

What 2 protease actions occur in this pathway during low fe to block hepcidin txn

A

Hjv degraded protease

Hjv cleavage of a soluble subunit which then binds to bmp6 and sequesters it outside of cell = no smad signalling

41
Q

To stop accumulation of fe in cell when ferroportin ia blocked, what happens

A

Down reg of dmt1 transporter
No irp binding = ferritin increase for storage, heme synthesis etc
Hif2a block of txn of usual genes like dmt and dcytb

42
Q

Ferroportin sexretion during excess fe in cell happens, which other export can get rid of fe in cell

A

Heme secretion

43
Q

How much fe can ferritin hold

A

4500 fe3

44
Q

What chaperone loads fe to ferritin

A

Pcbp1

45
Q

What is h ferritin for

A

Ferroxidase/ oxidises fe2 to fe3 for incorporation into ferritin

46
Q

What is phosphorylated when hepcidin binds ferroportin for internalisation and degradation

A

Jnk2

47
Q

What hormone ensures ferroportin is not blocked by hepcidin to get fe to weythroid cells

A

Erythropoietin

48
Q

What protease is blocked by the tfr2,hfe,fetf complex

A

Furin which cleaves soluble hjv part

49
Q

Where does the hepcidin txn regulation occur

A

In the liver

50
Q

What is the evidence for erk smad cross talk

A

Inhibition of erk blocks phos of smad 1,5 and 8

51
Q

Explain the pathogenesis of hemochromatosis

A

Disregulated fe absorption movement and deposition due to mutations in the Hepcidin/ferroportin pathway

52
Q

What sort of mutations causes it

A

Hepcidin itself, tfr2, ferroportin, hfe, hjv

53
Q

What is the opposite of it

A

Anemia where fe is deficient due to high hepcidin low ferroportin

Chronic Disease (16 decks)

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