6. Erythrocyte Biochemistry Flashcards
What is the main form of hemaglobin in a fetus?
α2γ2
What is the main form of hemaglobin in an adult?
α2β2
What element of heme carries O2?
Ferrous, Fe2+
How does the conformation of Hb change when O2 binds?
Iron moves into plane of porphyrin. This pulls the proximal histidine towards it and changes associated globin chain, leading to more O2 binding.
How does the Bohr Effect contribute to O2 release from Hb?
pH of actively respiring tissues is lower than average. This decrease in pH decreases the binding affinity of O2 on Hb (histadine binds H+). Conformational change favors relase of O2.
Which glycolytic intermediate reduces O2 affinity for Hb?
2,3-BPG
How come fetal Hb (HbF) has a higher affinity for O2?
It does not bind will to 2,3-BPG, which would normally reduce O2 affinity.
What amino acid mutation causes sickle cell anemia?
Glutamic acid (negative charge) changes to valine (hydrophobic). Causes cell to collapse on itself.
What are the two main molecules that store iron?
Ferritin and hemosiderin
How does iron enter the blood following the consumption of animal products?
Heme iron ferrous (Fe2+) is converted to ferric (Fe3+) by ferroxidase if being stored. If not, ferroportin transports Fe2+ out the RBC. Fe2+ is converted to Fe3+ outside the cell via ferroxidase then binds transferrin.
How does iron enter the blood following the consumption of plant products?
Fe3+ is converted to Fe2+ outside of RBC, then transferred inside via DMT1. Fe2+ is then transferred back outside the RBC via ferroportin. Fe2+ is converted to Fe3+ outside the cell via ferroxidase then binds transferrin.
How does hephaestin and hepcidin effect ferroportin’s function?
Hephaestin is required for the normal function of ferroportin.
Hepcidin binding causes internalization and degradation of ferroportin (regulatory).
How is iron bound to transferrin uptaken by a cell?
It is internalized via endocytosis by transferrin receptor (TfR). Low pH of endosome releases transferrin from its receptor. Endosome docks on mitochondria and transfers iron directly via DMT1.
How is hepcidin regulated?
When iron is high, hepcidin expression is up, ferroportin levels down, iron absorption low.
When iron is low, hepcidin expression is down, ferroportin levels up, iron absorption high.
What kind of anemia does iron deficiency cause?
Hypochromic microcytic anemia
What kind of anemia does iron overload cause? What mutation causes it?
Hereditary hemochromatosis
Caused by mutation in hereditary hemochromatosis gene (HFE)
What kind of anemia does deficiency in folate and vitamin B12 cause? How does this occur?
Megaloblastic anemia (large erythrocytes)
Occurs due to diminished synthesis of DNA
How is folate converted to the active form?
Folate is reduced to dihydrofolate (DHF) by dihydrofolate reductase. DHF is further reduced by dihydrofolate reductase to form tetrahydrofolate (THF), the active form.
What is tetrahydrofolate’s (THF) role in DNA?
It is important for the synthesis of purines and the pyrimidine thymine.
What is vitamin B12’s role in folate metabolism?
It transfers the methyl group off of THF
How does methotrexate work?
It is an inhibitor of dihydrofolate reductase. It binds with a much higher affinity than DHF. Inhibits DNA synthesis.
What molecule is at the center of vitamin B12?
Cobalt
What is the most common cause of vitamin B12 deficiency?
Lack of intrinsic factor (needed for B12 transportation)
What kind of anemia is caused by B12 deficiency due to lack of intrinsic factor (IF)?
Pernicious anemia (a type of magaloblastic macrocytic anemia)
