Erythrocyte Biochemistry

Question 1

describe the structure of adult hemoglobin

Answer 1

Hb A(alpha2beta2) tetramer
carries iron in ferrous form
Fe2+

Question 2

Why does sickle cell anemia not affect the fetus?

Answer 2

sickle cell anemia is caused by a alteration in aa #6 valine to glutamic acid ON THE BETA subunit

Question 3

What is the most stable secondary structure of amino acids? What is a sticky structure?

Answer 3

alpha helix is very stable,

beta sheets are sticky

Question 4

What is the bohr effect?

Answer 4

lower pH->less affinity to Hb

Question 5

how is iron stored in the body?

Answer 5

ferritin in liver

Question 6

What protein facilitates iron transport in the body?

Answer 6

transferrin

Question 7

What form is dietary iron?

Answer 7

ferric

Question 8

What is the first step in transport of iron in gut epithelium?

Answer 8

reduction of iron by cytochrome b

Question 9

What transporter facilitates uptake of iron from gut lumen?

Answer 9

DMT1

Question 10

What transporter facilitates transport of iron from the gut to the blood? What does it require to function?

Answer 10

ferroportin
requires ferroxidase (hephaestin)

Question 11

What keeps body safe from toxic iron?

Answer 11

transferrin binds to Fe3+ with high affinity and delivers it safely to tissues

Question 12

How and where is blood iron transported (target location)?

Answer 12

erythroblasts have TfR (receptors)
after binding->endosome develops and takes it directly to mitochondria;
DMT1 transports iron out of endosome, then iron is again reduced (ferrireductase)

Question 13

Where is iron reduced/oxidized in the body?

Answer 13

in gut to Fe2+, in blood to Fe3+, in mitochondria to Fe2+

Question 14

describe hepcidin

Answer 14

made by liver; binds to ferroportin and causes proteolysis; if Fe high then hepcidin raised and ferroportin levels down

Question 15

What regulates hepcidin expression?

Answer 15

Hfe binds to receptors for the hepcidin signalling complex (eventual hepcidin transcription), and when transferrin (with Fe) also binds, then it turns on the signal transduction pathway to generate hepcidin

Question 16

describe folate metabolism

Answer 16

DHF reduced to THF by DHF reductase

THF is active form that transfers C from donors to acceptors (purines)

Question 17

Why is cobalamin needed?

Answer 17

B12 is required to convert N5-methyl THF to active THF

Then transfers the methyl to homosysteine

Question 18

A deficiency in THF or B12 can cause what?

Answer 18

megaloblastic macrocytic anemia

Question 19

How is cobalamin absorbed?

Answer 19

R binder proteins bind to b12;
IF (intrinsic factor made in stomach parietal cells) and proteases(pancreas) cause R binders to release B12 which then binds to IF;
IF carries B12 to ileum to be absorbed by cubulin (endocytosis)
transcobalamin carries B12 in the blood

Question 20

what is a significant cause of pernicious anemia that relates to cobalamin?

Answer 20

IF is destroyed as well as the stomach parietal cells that produce it via auto-immune mechanisms (Intrinsic Factor BTW)

Question 21

Describe Schilling test

Answer 21

1- label B12, inject labeled (give normal orally), then collect urine
2-if absent in urine then proceed to part three, if present then b12 is deficient in the diet
3-give injection of unlabeled and give labeled orally
4-if radioactive b12 present in urine then lacks IF