Iron

Question 1

Transferrin receptors (3)

Answer 1

Major regulatory system for Fe going into cells
Membranes Tf receptors number of proportional to uptake of Fe
Iron deficiency increase TfR gene transcription by 2-3 fold

Question 2

Ferritin storage (3)

Answer 2

Protects of cells against toxic effect of iron
Ferritin production is directly coupled to iron status
Through changes in ferritin mRNA translation

Question 3

IRP TfR (5)

Answer 3

IREs indirectly modulates TfR mRNA translation
By influencing rate of degradation
TfR mRNA have 3 IREs in their 3’ UTR
Binding of IRP to IRE retards mRNA degradation
mRNA stability is changed because a dramatic change in expression is required

Question 4

How may erythropoiesis regulate iron homeostasis (4)

Answer 4

Absorption changes in response to erythropoiesis requirement
High requirement increases iron absorption
Hepidicin is thought to be high when iron is high
And interacts with ferroportin to prevent iron transport

Question 5

Iron homeostasis theory (5)

Answer 5

Mucosal theory suggests that saturated ferritin prevents more absorption of iron

Another theory is that irons absorption changes in response to total body iron
Low iron status may signal a change in ferritin
And DMT1 levels
In crypt cells

Question 6

IRPs ferritin effects (4)

Answer 6

Ferritin mRNAs have a single IRE in their 5’ UTR
IRPs bind to IRE in ferritin mRNA
Prevents association of 43S pre initiation complex with 5’UTR
And blocks translation

Question 7

IRP2 (7)

Answer 7

Similar peptide sequence to IRP1
But has a 73 AA insertion
IRP2 degradation is increased in the presence of iron
The 73 AA sequence is a signal for degradation of IRP2
Iron induces oxidation of IRP2
Leading to proteolysis
Removal of 73 AA sequence stabilises IRP2 from degradation

Question 8

IRP 1 (4)

Answer 8

Also functions as the enzyme aconitase
The change from RNA binding protein to aconitase is dependent on the presence of ferric iron
This change occurs without changes in total amount of protein
When iron levels drop there is a high affinity for RNA

Question 9

Iron intro (4)

Answer 9

Plays a role in several biochemical processes
This includes energy
Oxygen transport
And cell growth

Question 10

How is iron tightly regulated (4)

Answer 10

Bound to functional proteins such as in:
Haemoglobin and myoglobin
Transport iron like transferrin and storage proteins like ferritin

Question 11

Post-transcriptional regulation of iron and selenium (4)

Answer 11

Alter translation of mRNA
Or stability of protein

Increase the level of mRNA can be achieved by:
Increasing transcription from the gene
Decreasing the degradation of mRNA

Question 12

Iron regulatory element (5)

Answer 12

28 nucleotide sequence 
In RNA sequence 
Stem loop with 6 nucleotides 
Bound by IRPs
In iron limiting conditions

Question 13

Iron basolateral membrane (3)

Answer 13

Ferric iron converted to ferrous iron
Binds to transferrin
TfR regulates transferrin ferrous iron uptake

Question 14

Iron enterocyte absorption (5)

Answer 14

Iron absorbed into duodenum
Ferric iron absorbed into enterocyte by DMT1
Ferrous by HCP1
Within enterocyte excess ferric iron bound to ferritin
Absorbed ferric iron transported to basolateral membrane