Iron and heme

Question 1

small RBCs is a clue for what type of iron dysfunction?

Answer 1

uptake dysfunction

Question 2

what is the mechanism of the Fenton reaction?

Answer 2

1. oxygen picks up electron from iron or copper
2. iron / copper oxidized
3. superoxide anion or hydroxyl radical produced

Question 3

what are the active forms of iron?

Answer 3

Hb, Mb, cytochromes

Question 4

iron is transported by what protein?

Answer 4

transferrin

Question 5

what is the inactive form of iron?

Answer 5

ferritin

Question 6

what is the degenerated, long term storage of iron?

Answer 6

hemosiderin

Question 7

what cells are the gatekeepers of iron uptake?

Answer 7

enterocytes

Question 8

what is the role of divalent methyl transporter (DMT)?

Answer 8

uptake of iron 2+

Question 9

what is the role of cytochrome B on the enterocyte?

Answer 9

reduces Fe 3+ to 2+ for uptake

Question 10

inside the cell, iron is protected by what protein?

Answer 10

ferritin

Question 11

what is the role of ferroportin?

Answer 11

determines how much iron will be released from enterocyte into circulation

Question 12

what is the role of hepcidin?

Answer 12

downregulates activity of ferroportin - blocks uptake of iron

Question 13

what is the role of hephaestin?

Answer 13

oxidizes iron 2+ to 3+ to be taken up by ferritin in the circulation

Question 14

iron is taken up into other cells by what mechanism?

Answer 14

transferrin receptors

Question 15

the presence of hemosiderin indicates what condition?

Answer 15

iron overload

Question 16

in a hemolytic disorder involving destruction of RBCs inside macrophages, what happens to the ferritin?

Answer 16

accumulates then degrades to hemosiderin

Question 17

what is the main regulator of iron uptake?

Answer 17

hepcidin

Question 18

how does low hepcidin affect iron uptake?

Answer 18

high uptake

Question 19

a defect in what enzyme results in hereditary hemochramotosis? how?

Answer 19

1. human hemochromatosis protein (HFE)

2. low hepcidin production

Question 20

regulation of intracellular iron storage occurs at what level?

Answer 20

post transcription

Question 21

what is the role of iron response elements (IREs)?

Answer 21

forms hairpin loop on mRNA for ferritin that prohibits the placement of the ribosome at the start codon (prohibiting transcription of iron binding factors)

Question 22

what is the role of aconitase?

Answer 22

iron regulatory protein that is bound to the IRE in low iron conditions (do not need ferritin when there is already low iron)

Question 23

what is the result of free iron on the IREs?

Answer 23

1. binds aconitase and removes it from the IRE

2. translation of ferritin can begin

Question 24

where are IREs found?

Answer 24

1. ferritin RNA
2. ALA synthase RNA
3. transferrin receptor RNA

Question 25

what is the key enzyme for heme synthesis?

Answer 25

ALA synthase

Question 26

what is the function of the IRE on the transferrin receptor?

Answer 26

repression of translation (if cell is already full of iron then you want to shut down receptors so you are not taking up more)

Question 27

what does total iron binding capacity (TIBC) measure?

Answer 27

unoccupied transferrin

Question 28

how does a high TIBC level relate to iron stores?

Answer 28

high TIBC = low iron stores

Question 29

what does transferrin saturation measure?

Answer 29

occupied transferrin

Question 30

how does a high transferrin saturation relate to iron stores?

Answer 30

high saturation = high iron stores

Question 31

what is the best measure of iron body stores?

Answer 31

serum ferritin

Question 32

what is protoporphyrin?

Answer 32

iron-free precursor of heme

Question 33

what does a high protoporphyrin level indicate?

Answer 33

low iron stores (not enough to load all the heme)

Question 34

iron deficiency can develop into anemia via what mechanisms?

Answer 34

1. iron depletion 2. deficient erythropoiesis 3. low Hb (hypochromia, microcytosis)

Question 35

iron overload is characterized by what findings?

Answer 35

1. high transferrin saturation | 2. hemosiderin deposits

Question 36

heme synthesis starts with what compounds?

Answer 36

succinyl CoA and glycine

Question 37

which compound in heme synthesis is photoactive?

Answer 37

UPG3

Question 38

definition: porphyrias

Answer 38

heme synthesis disorders

Question 39

what is the precursor to UPG3? is it photoactive?

Answer 39

1. porphobilinogen | 2. no

Question 40

acute intermittent porphyria is a build up of what heme precursor? is it a photoactive disorder?

Answer 40

1. porphobilinogen | 2. no

Question 41

how does AIP affect the urine? blood?

Answer 41

1. dark red urine (accumulation of PBG and ALA) | 2. anemia (cannot make enough heme)

Question 42

porphyria cutanea tarda is a build up of what heme precursor? is it a photoactive disorder?

Answer 42

1. UPG3 | 2. yes

Question 43

lead poisoning affects what steps of heme synthesis?

Answer 43

1. PBG synthase (ALA to porphobilinogen) | 2. ferrochelatase

Question 44

which porphyria is exacerbated by alcohol consumption (stress)?

Answer 44

AIP (acute intermittent porphyria)

Question 45

what regulates ALA synthase?

Answer 45

heme