Erythrocyte Biochemistry Flashcards
describe the structure of adult hemoglobin
Hb A(alpha2beta2) tetramer
carries iron in ferrous form
Fe2+
Why does sickle cell anemia not affect the fetus?
sickle cell anemia is caused by a alteration in aa #6 valine to glutamic acid ON THE BETA subunit
What is the most stable secondary structure of amino acids? What is a sticky structure?
alpha helix is very stable,
beta sheets are sticky
What is the bohr effect?
lower pH->less affinity to Hb
how is iron stored in the body?
ferritin in liver
What protein facilitates iron transport in the body?
transferrin
What form is dietary iron?
ferric
What is the first step in transport of iron in gut epithelium?
reduction of iron by cytochrome b
What transporter facilitates uptake of iron from gut lumen?
DMT1
What transporter facilitates transport of iron from the gut to the blood? What does it require to function?
ferroportin requires ferroxidase (hephaestin)
What keeps body safe from toxic iron?
transferrin binds to Fe3+ with high affinity and delivers it safely to tissues
How and where is blood iron transported (target location)?
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)
Where is iron reduced/oxidized in the body?
in gut to Fe2+, in blood to Fe3+, in mitochondria to Fe2+
describe hepcidin
made by liver; binds to ferroportin and causes proteolysis; if Fe high then hepcidin raised and ferroportin levels down
What regulates hepcidin expression?
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
describe folate metabolism
DHF reduced to THF by DHF reductase
THF is active form that transfers C from donors to acceptors (purines)
Why is cobalamin needed?
B12 is required to convert N5-methyl THF to active THF
Then transfers the methyl to homosysteine
A deficiency in THF or B12 can cause what?
megaloblastic macrocytic anemia
How is cobalamin absorbed?
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
what is a significant cause of pernicious anemia that relates to cobalamin?
IF is destroyed as well as the stomach parietal cells that produce it via auto-immune mechanisms (Intrinsic Factor BTW)
Describe Schilling test
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
