Erythrocyte Biochemistry - Staudinger

Question 1

What are the two variants of adult hemoglobin? What is the fetal variant of hemoglobin? 4

Answer 1

Adult:
α2β2 - 97%
α2δ2 - 3%

Fetal:
α2γ2

Question 2

What is the mutation occurring in sickle cell anemia

Answer 2

Glutamic acid (Glu) –> Val
Negative Neutral
Hydrophilic Hydrophobic

Question 3

What is the effect of 2,3-BPG on hemoglobin

Answer 3

Reduces the O2 affinity for hemoglobin

Question 4

What is positive cooperatively?

Answer 4

Hemoglobin binds O2 in a cooperative fashion. Each binding facilitates the next binding

Question 5

What is the effect of pH on oxygen binding to hemoglobin? 10

Answer 5

Affinity for oxygen decreases with a decrease in pH (oxygen off-loading O2 in high CO2 environments)

Question 6

Why does fetal hemoglobin have such a high affinity for oxygen? 11

Answer 6

2,3-BPG does not bind well to the gamma subunit of hemoglobin therefore oxygen affinity is increased

Question 7

What form is iron stored in the liver as?

Answer 7

Ferritin

Question 8

What form is iron in our diet?

Answer 8

Fe3+ (ferric form)

Question 9

What converts iron from Fe3+ –> Fe2+?

Answer 9

Dcytb (duodenal Cytochrome b)

Question 10

What transports Fe2+ into the enterocyte? 19

Answer 10

DMT1

Question 11

What form of iron does transferrin transport? 20

Answer 11

Fe3+

Question 12

What disease does iron deficiency result in? 22

Answer 12

Hypochromic macrocytic anemia

Question 13

What occurs in hereditary hemochromatosis? 23

Answer 13

An excess of 15g of iron in the blood (normal –> 3-5g)

Question 14

What is the role of hepcidin? 24

Answer 14

When high [Fe2+]
Hepicidin activity high
Ferroportin levels down

When low [Fe2+]
Hepcidin activity low
Ferroportin levels high

Question 15

What is the role of hepcidin? 24

Answer 15

Binds to ferroportin and causes internalization of ferroportin into the enterocyte

Question 16

What cofactors are required for RBC production? 27

Answer 16

Vitamin B12 - cobalamin

Folate

Question 17

What causes megaloblastic anemia? 27

Answer 17

Deficiency of vitamin B12 and Folate

Question 18

What is the first step in folate metabolism? 31

Answer 18

Reduction to THF by dihydrofolate reductase

Question 19

What is the active form of Folate? 32

Answer 19

Tetrahydrofolate –> transfers carbon units from donors to acceptors (DNA syn)

Question 20

What is referred to as a folate trap? 36

Answer 20

Occurs when B12 is not available resulting in folate staying as N5-methyl-THF

Question 21

What does B12 do to N5-methyl-THF (folate)? 37

Answer 21

B12 removes the methyl group making:

THF (also called FH4)
B12-CH3

Question 22

What happens when B12 enters the stomach? 39

Answer 22

B12 is bound by R Binders

Pepsin digests the complex and intrinsic factor binds B12

Intrinsic factor carries B12 to the ileum where receptors bring it into he body

Question 23

What is the purpose of the shilling test? 43

Answer 23

To tell whether a B12 deficiency is due to problems with diet or absorption

Question 24

What is the procedure during the schilling test? 43, 44

Answer 24

If Dietary:
Radioactively labeled cobalmin (B12) ingested, if shows up in urine the problem is dietary

If absorption:
Above procedure will not yield any B12 in the urine

repeat test with radioactively labeled cobalmin AND intrinsic factor

Question 25

What causes Pernicious anemia? 41

Answer 25

Vitamin B12 deficiency due to a lack of intrinsic factor