Lecture 6: Erythrocyte Biochemistry Flashcards
How does the structure of hemoglobin differ between adult and fetal forms?
Adult: 2 alpha and 2 beta globin chains
Fetal: 2 alpha and 2 gamma globin chains
What state is the iron atom in a heme?
Fe 2+ (ferrous)
When oxygen binds to a heme group, what happens to iron ion?
Iron movies into plane of heme and pulls down the proximal histidine of hemoglobin
-oxygen forms a hydrogen bond with histidine
What type of oxygen saturation curve is seen with a myoglobin?
Hyperbolic curve
-only 1 peptide
What type of oxygen saturation curve is seen with a hemoglobin?
Sigmoidal curve
-due to interaction between four globin subunits
Describe positive cooperativity.
The binding of one oxygen molecule to hemoglobin makes it easier to bind to other oxygen molecules
-change in one globulin subunit induces a change in another subunit
What is the Bohr Effect?
Decreased affinity of hemoglobin for oxygen
-releases oxygen (want this in tissues)
What changes are seen in Bohr Effect?
1) Decrease in pH (increase in H+)
2) Increase in 2,3-BPG (tells Hb to give up oxygen)
3) Exercise (drop in partial pressure of oxygen)
Why is affinity for oxygen higher in fetal red cells compared to maternal red cells?
Fetus needs to get oxygen from mother
- fetal Hb does not bind well to 2,3-BPG
- left shift
In sickle cell disease, where is the mutation?
Amino Acid position #6 in beta globulin
- glutamic acid changes to valine
- polymerization of hemoglobin
Where is iron stored?
- Cells that line intestine
- Liver
- Spleen
- Bone Marrow
How is heme iron stored?
1) Fe 2+ (heme) enters enterocyte (intestinal cell) and converted into Fe 3+ via ferroxidase
2) Stored as ferritin and can be degraded into hemosiderin
How is non-heme iron stored?
1) Fe 3+ is converted into Fe 2+ in the intestinal lumen via ferric reductase in presence of Vit C
2) Fe 2+ enters enterocyte via DMT1
3) Fe 2+ is converted into Fe 3+ via ferroxidase
4) Stored as ferritin and can be degraded into hemosiderin
How does iron leave the enterocyte?
1) Must be in Fe 2+ state
2) Leaves basolateral side via ferroportin.
3) Converted to Fe 3+ via ferroxidase
4) Transferrin transports Fe 3+ to liver, spleen, bone marrow
Ferroportin requires what for its function?
Hephaestin
Ferroportin levels and iron content in the body are regulated by?
Hepcidin
Describe the process of transferrin uptake.
1) Uptake via receptor-mediated endocytosis via transferrin receptor
2) Internalized via clathrin pits
3) Transferrin is released in endosome due to low pH
4) Iron is uptaken in mitochondria via DMT1
What happens when hepcidin binds to ferroportin?
Internalization of ferroportin and subsequent degradation in lysosomes
What regulates levels of hepcidin?
Transferrin and its receptor: Human homeostatic iron regulator protein (HFE)
- High levels of iron (transferrin)n–> hepcidin expression up –> low levels of ferroportin –> low iron absorption levels
- Low levels of iron (transferrin) –> hepcidin expression down –> high levels of ferroportin –> high iron absorption levels
What can cause iron deficiency?
- Insufficient dietary iron
- Insufficient absorption
- Excessive blood loss via menstruation
- Overuse of aspirin
- Ulcers of GI tract
What can iron deficiency cause?
Hypochromic microcytic anemia
What can iron overload cause?
Hereditary Hemochromatosis
- accumulation of iron in heart, liver, and pancreas, which can cause severe issues
- autosomal recessive in HFE gene
- 15 g of iron instead of normal 3-5
RBC production is dependent on what?
Folate Vitamin B12 (cobalamin)
What can a deficiency in folate and vitamin B12 cause?
Megaloblastic anemia
- diminished synthesis of DNA
- large RBC
