Erythrocyte Biochemistry Flashcards
(25 cards)
During phase 1 of the developmental pathway of erythropoiesis, what is unregulated?
Ribosome synthesis!
So we can make a bunch of hemoglobin
Describe the structure of Hemoglobin
2 alpha-globin chains
2 beta-globin chains
One heme per subunit with a central Fe2+
Hydrophobic
F8 histidine»proximal histidine—bound to heme
E7 histidine»distal histidine—stabilizes O2 that binds to heme
Conformational change when O2 binds»flattens
What chains are found in HbF and HbA?
Hb F»alpha2, gamma2
HbA»alpha2, beta2
What kind of research is being done to treat sickle cell?
Inducing expression of HbF
What do they use to induce HbF currently
Hydroxyurea, but this is toxic.
Myoglobin vs hemoglobin
Myoglobin is a monomer and has a hyperbolic oxygen dissociation curve.
Hemoglobin is a tetramer of subunits. It has a sigmoidal oxygen dissociation curve due to positive cooperativity.
What does 2,3-BPG do?
Reduces O2 affinity so that Hb gives up more O2 to tissues.
What can also contribute to changing affinity in hemoglobin?
pH of actively respiring tissues is lower, making affinity for O2 lower, so it will oxygenate the tissue.
Histidine 146 pick up H+ from acidic tissues to help heme let go of O2
27% of iron is stored in the body.
How?
As ferritin (H20 soluble) And as hemosiderin (H2O insoluble)
Describe the steps of iron absorption
- Ferric reductase (dcytb) converts non heme Ferric (Fe3) to ferrous (Fe2) with the help of vitamin C
- divalent transporter 1 takes Fe2+ into the cell.
- ferry port in exports Fe2 out of the cell.
- ferroxidase changes fe2 to fe3
- chelates, now Fe3+Fe3 as transferrin. This is the man form of iron in the body.
What protein allows Fe2+ to be transferred to the basolateral side of the enterocyte?
What peptide hormone regulates this protein?
Ferroportin
Hepcidin marks ferroportin for endocytosis, decreasing the amount of iron that is absorbed.
How is transferrin brought into the cell?
Receptor mediated endocytosis!
Transferrin binds, internalized by clathrin coated pits.
Endosome can dock on the mitochondria and deposit iron directly into it.
What does an iron deficiency cause?
Hypochromic microcytic anemia.
Not enough Hb in the cell, doesn’t stain very well.
Treat with dietary iron supplement.
Describe Hereditary Hemochromatosis
Autosomal recessive mutation that causes dysfunctional regulation of iron absorption.
Causes iron overload.
Normal body iron is 3-5g.
Affected have 15g
Describe the regulation of iron via hepcidin in low and high iron levels.
Iron high: hepcidin expression up, ferroportin levels down, iron absorption low.
Iron Low: hepcidin expression down, ferroportin levels up, iron absorption high.
What two vitamins are intregal to RBC production?
What does a deficiency of these cause?
Cobalamin and folic acid.
Cause megaloblastic anemia.
Impairs DNA synthesis.
Describe megaloblastic macrocytic anemia cells
- large erythrocytes
- normal Hb content in relation to size
- normochromic cells on stain
- in bone marrow—large cells, hyper-segmented neutrophils
How many parts does folate have?
3!
What is the active form of folate?
What can it do?
THF, Tetrahydrofolate
It can grab and donate carbons.
What sucks about methyl-THF?
It cannot be converted back to THF without cobolamin
Why do we need cobolamin to absorb folic acid in the intestine?
In the intestine, dietary folic acid is reduced to methyl-THF, and needs cobolamin to make it into its active form again.
What does cobalamin do with the methyl it takes off methyl-THF?
Transfers it to homocysteine to make methionine via methionine synthase
Describe how B12 is absorbed
- dietary B12 binds to R-binder proteins made by the gastric mucosa
- proteases made by the pancreas degrade R-binder.
- B12 now binds to intrinsic factors made by parietal cells.
- intrinsic factor carries B12 to the ileum where it will be absorbed.
How is cobalamin circulated through the blood?
It is carried by transcobalamin
