Erythrocyte Biochemistry Flashcards
What form of Iron does Heme carry?
Ferrous: Fe2+
What are the specific subunits for fetal hemoglobin?
HbF (alpha2, gamma2)
What is the current toxic chemotherapeutic agent used in research to induce HbF?
Hydroxyurea
What is the Proximal Histidine and what does it bind to?
F8 Histidine. It binds to heme.
What is the Distal Histidine and what does it bind to?
E7 Histidine: Oxygen binds to the iron between the heme and the distal histidine.
The binding of Oxygen to Fe of a global subunit pulls the ___________Histidine down.
Proximal F8
What are the 2 molecules used to store Iron? Which one is water soluble?
- Ferritin: water soluble
2. Hemosiderin: water insoluble.
What is the function of Ferric Reductase?
converts Fe3+ in non-heme iron(from plant products) to Fe2+
What is the function of DMT1(Divalent Transporter-1)
takes up Fe2+ into enterocyte
What is the function of Ferroportin?
Transports Fe2+ from enterocyte to the outside of the cell (blood and circulation).
What does Ferroportin require to transport iron to the outside of the cell(blood)?
Ferroxidase (Hephaestin, Cerruloplasmin).
What is the function of Hephaestin (Cerruloplasmin, Ferroxidase)?
Converts free iron( Fe2+) to Fe3+
What is the function of Transferrin?
Transports Iron (Fe3+) in the blood to bone marrow.
What peptide hormone regulates absorption of Iron?
Hepcidin
How does uptake of Tranferrin occur?
by receptor-mediated Endocytosis via transferrin receptors (TfR).
Internalized via clathrin coated pits(endosomes).
What is Hereditary Hemochromatosis?
It is an organ dysfunction due to Iron overload: cirrhosis, arthritis, skin pigmentation, cardiomyopathy.
Treatment is blood letting.
What is the receptor of Hepcidin and how does it control it?
Ferroportin.
Binding of Hepcidin to Ferroportin causes internalization of Ferroportin; it is destroyed by proteolysis. Therefore, when Hepcidin expression is up, Ferroportin levels are down.
What is Megaloblastic Macrocytic Anemia and what causes it?
Large erythrocytes/erythroblasts(megaloblasts). also hyper segmented neutrophils occur( more than 5 lobes-usually 3 to 4).
It is caused by a deficiency in Folic acid and Vitamin B12(Cobalamin).
Also occurs due to a diminished synthesis of DNA in developing RBCs in bone marrow.
What are the 3 parts of Folic Acid?
- Pteridine ring
- PABA
- Glutamate residues chains
What is the active form of Folate?
THF(tetrahydrofolate)
What reduces Dihydrofolate to Tetrahydrofolate?
Dihydrofolate reductase
What is the function of THF? In which process does it serve a VITAL role?
It transfers Carbon units from donors to acceptors.
Serves a vital role in DNA synthesis.
When does the main Carbon transfer occur in the Folate Metabolism?
When the Carbon side chain of Serine is transferred to THF; forms N5,10-methyle THF. This carbon is then transferred to dUMP to form dTMP.
Deficiency of Folic acid leads to_________
decrease in synthesis of DNA which leads to Megaloblastic Macrocytic Anemia.
Where is Folic acid absorbed in the body?
In the small intestine: Jejunum.
What is the primary form of THF in bloodstream? (this is also the same form as the THF that gets reduced in the intestine)
N5-methyl THF.
What does N5-methyl THF require in order to be demethylated?
Requires Vitamin B12.
What is a very important function of Vitamin B12(Cobalamin) duringg the Folate cycle?
It removes methyl group from N5-methyl THF to activate it.
How is B12 absorbed?
B 12 bind to R-binder protein (made by the gastric mucosa cells). Intrinsic factors (made by parietal cella of stomach) carry B12 to Ileum where receptors bring it into body. (endocytosis)
Cobalamin circulates through the blood carried by_____?
Transcobalamin
What is Pernicious Anemia?
A Megaloblastic Macrocytic Anemia caused by a B12 deficiency (from unavailability of Intrinsic factors).
