6. Erythrocyte Biochemistry

Question 1

What is the main form of hemaglobin in a fetus?

Answer 1

α2γ2

Question 2

What is the main form of hemaglobin in an adult?

Answer 2

α2β2

Question 3

What element of heme carries O2?

Answer 3

Ferrous, Fe2+

Question 4

How does the conformation of Hb change when O2 binds?

Answer 4

Iron moves into plane of porphyrin. This pulls the proximal histidine towards it and changes associated globin chain, leading to more O2 binding.

Question 5

How does the Bohr Effect contribute to O2 release from Hb?

Answer 5

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.

Question 6

Which glycolytic intermediate reduces O2 affinity for Hb?

Answer 6

2,3-BPG

Question 7

How come fetal Hb (HbF) has a higher affinity for O2?

Answer 7

It does not bind will to 2,3-BPG, which would normally reduce O2 affinity.

Question 8

What amino acid mutation causes sickle cell anemia?

Answer 8

Glutamic acid (negative charge) changes to valine (hydrophobic). Causes cell to collapse on itself.

Question 9

What are the two main molecules that store iron?

Answer 9

Ferritin and hemosiderin

Question 10

How does iron enter the blood following the consumption of animal products?

Answer 10

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.

Question 11

How does iron enter the blood following the consumption of plant products?

Answer 11

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.

Question 12

How does hephaestin and hepcidin effect ferroportin’s function?

Answer 12

Hephaestin is required for the normal function of ferroportin.

Hepcidin binding causes internalization and degradation of ferroportin (regulatory).

Question 13

How is iron bound to transferrin uptaken by a cell?

Answer 13

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.

Question 14

How is hepcidin regulated?

Answer 14

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.

Question 15

What kind of anemia does iron deficiency cause?

Answer 15

Hypochromic microcytic anemia

Question 16

What kind of anemia does iron overload cause? What mutation causes it?

Answer 16

Hereditary hemochromatosis

Caused by mutation in hereditary hemochromatosis gene (HFE)

Question 17

What kind of anemia does deficiency in folate and vitamin B12 cause? How does this occur?

Answer 17

Megaloblastic anemia (large erythrocytes)

Occurs due to diminished synthesis of DNA

Question 18

How is folate converted to the active form?

Answer 18

Folate is reduced to dihydrofolate (DHF) by dihydrofolate reductase. DHF is further reduced by dihydrofolate reductase to form tetrahydrofolate (THF), the active form.

Question 19

What is tetrahydrofolate’s (THF) role in DNA?

Answer 19

It is important for the synthesis of purines and the pyrimidine thymine.

Question 20

What is vitamin B12’s role in folate metabolism?

Answer 20

It transfers the methyl group off of THF

Question 21

How does methotrexate work?

Answer 21

It is an inhibitor of dihydrofolate reductase. It binds with a much higher affinity than DHF. Inhibits DNA synthesis.

Question 22

What molecule is at the center of vitamin B12?

Answer 22

Cobalt

Question 23

What is the most common cause of vitamin B12 deficiency?

Answer 23

Lack of intrinsic factor (needed for B12 transportation)

Question 24

What kind of anemia is caused by B12 deficiency due to lack of intrinsic factor (IF)?

Answer 24

Pernicious anemia (a type of magaloblastic macrocytic anemia)

Question 25

How does one determine if a patient has pernicious anemia vs magaloblastic macroytic anemia?

Answer 25

Schilling test

Tests for absorption of B12 with radioactive cobalt. If absent, IF is added. If there’s absorption after IF added, then patient has pernicious anemia.