Erythrocyte Biochemistry

Question 1

How much total body iron is normal?

How much iron is there in hereditary hemochromatosis?

Answer 1

3 - 5g

15 g

Question 2

What is the F8 histidine?

Answer 2

Proximal histidine = bound to heme

Question 3

What does ferritin degrade into?

What is important about this molecule?

Answer 3

hemosiderin

It is insoluble, while ferritin is soluble

Question 4

What is the E7 histidine?

Answer 4

distal histidine = O2 binds the iron btw heme and distal histidine (sandwiched btw heme and E7) –> conformational change

Question 5

What are the 3 parts of folic acid?

Answer 5

Pteridine
PABA
glutamate

Question 6

What causes megaloblastic macrocytic anemia?

Answer 6

B12 or folate deficieny –> diminished syntheis of DNA –> large erythrocytes, but not enough of them

Question 7

What is the other type of adult hemoglobin?

What is it made of?

Answer 7

Hb A2 = 3% of hb in body

2 alpha, 2 delta

Question 8

What does B12 bind to in the stomach?

Where do these come from?

Answer 8

R-binders

made by gastric mucosa cells

Question 9

Where is heme synthesized in a cell?

What makes its uptake there so efficient?

Answer 9

mitochondria

Endosome can dock on mitochondria and tranfer iron directly w/out any cytoplasmic proteins

Question 10

What do you call iron in the blood?

Answer 10

transferrin

Question 11

What side is the basolateral side of the enterocyte?

Answer 11

Side touching blood

Question 12

What is the main adult hemoglobin called?

What is it made of?

Answer 12

Hb A

2 alpha and 2 beta chains = tetramer

Question 13

What carries vitamin B12 through the blood?

Answer 13

transcobalamin

Question 14

What are the two storage forms of iron?

Answer 14

ferritin = soluble
hemosiderin = insoluble

Question 15

What chromosomes do the genes come from that encode for hemoglobin?

Answer 15

16 and 11

Question 16

What molecule inhibits ferroportin to maintain optimum levels of iron in the blood?

Answer 16

Hepcidin –> causes internalization of ferroportin and destruction by proteolysis

Question 17

What are the embryonic hemoglobins?

Answer 17

Gower 1
Gower 2
Portland

Question 18

What form of iron is found in heme?

Answer 18

ferrous = Fe2+

Question 19

What does myoglobin’s oxygen dissociation curve look like?

What does hemoglobins curve look like?

Answer 19

hyperbolic

sigmoidal (due to 2 affinity states)

Question 20

When the pH drops, what specifically happens to Hb to cause release of O2?

Answer 20

His picks up H+ –> conformational change –> release of O2

Question 21

What causes hypochromic microcytic anemia?

Answer 21

iron deficiency

Question 22

What is pernicious anemia?

Answer 22

vit B12 deficiency that causes megaloblastic macrocytic anemia
due to lack of intrinsic factor

Question 23

When is the majority of hemoglobin synthesized in RBC production?

Answer 23

before extrusion of nucleus

small amount made in reticulocyte

Question 24

Why does fetal Hb have a higher affinity for O2 than maternal Hb

Answer 24

HbF does not bind well to 2,3-BPG –> signal to release oxygen isn’t registered, so it keeps O2 more than HbA would

Question 25

How is intrinsic factor-cobalamin taken up?

Answer 25

receptor-mediated endocytosis

Question 26

What is being researched now as a potential treatment for sickle cell anemia?

Answer 26

induce expression of HbF (fetal hemoglobin) | currently using hydroxyurea (chemotherapy), but trying to find other ways

Question 27

What does ferroxidase do? What is its other name? What is its co-factor?

Answer 27

Turns Fe2+ into Fe3+ in the blood ceruloplasmin Cu

Question 28

Where do you get Vit B12 in your diet?

Answer 28

animal products | microorganisms actually make the B12 - no animals can

Question 29

How many heme molecules are in a molecule of hemoglobin?

Answer 29

4 = 1 per subunit

Question 30

Where is folic acid absorbed?

Answer 30

small intestine (jejunum)

Question 31

What form of iron turns into ferritin for storage? | Where does this occur?

Answer 31

Fe3+ | in enterocyte

Question 32

When are embryonic hemoglobins "done"?

Answer 32

After week 8 of pregnancy

Question 33

What happens to R-binder proteins in the duodenum?

Answer 33

Proteases from the pancreas degrade R-binders --> B12 free

Question 34

What subunit of hemoglobin is deformed in sickle cell anemia?

Answer 34

beta globin

Question 35

What is hereditary hemochromatosis? | What is the treatment?

Answer 35

Iron overload from genetic mutation | blood letting

Question 36

What does ferroportin do?

Answer 36

transports Fe2+ (ferrous iron) from enterocyte into blood

Question 37

What makes intrinsic factor? | What does it do and where?

Answer 37

Parietal cells make it | Binds B12 after R-binders release it in duodenum --> carries b12 to ileum

Question 38

What form of iron is in Transferrin?

Answer 38

Fe3+ | I think 2 molecules per transferrin?

Question 39

What is the Bohr Effect?

Answer 39

How pH affects O2 affinity: as pH drops, affinity of Hb for O2 drops too! How Hb gives tissues O2

Question 40

Which form of folate can give carbons to DNA?

Answer 40

methylene

Question 41

Which form of folate do you get "stuck" at? | What do you need to turn it back into THF?

Answer 41

methyl | cobalamin (B12)

Question 42

What do you see in the bone marrow in megaloblastic macrocytic anemia?

Answer 42

large erythroblasts | also hyper-segmented neutrophils

Question 43

What enzyme converts Fe3+ (from plants) into Fe2+ in the intestinal lumen? What co enzyme is needed for this?

Answer 43

Ferric reductase, otherwise known as duodenal cyt. B | Vitamin C!

Question 44

An increase in what molecule causes Hb to have reduced affinity for O2 in addition to pH lowering?

Answer 44

2,3-BPG

Question 45

How much folic acid does the liver store? | How long would this last you?

Answer 45

5-10 mg | 3-6 months

Question 46

How is transferrin transported into cells for heme synthesis?

Answer 46

by receptor-mediated endocytosis via TfR

Question 47

What side is the apical side of the enterocyte?

Answer 47

side on intestinal lumen

Question 48

What molecule signals hepcidin synthesis when Tf-Fe binds to its receptor?

Answer 48

Hfe (Hephaestin?) | Tf-Fe--> Hfe+Tfr1 complex -->Hfe goes to Tfr2 -->Hepcidin production signalled

Question 49

How do you test for lack of intrinsic factor?

Answer 49

Schilling test

Question 50

Where does transferrin end up?

Answer 50

liver spleen bone marrow

Question 51

What does divalent transporter-1 (DMT1) do?

Answer 51

Takes Fe2+ into enterocyte from the intestinal lumen

Question 52

What is the fetal hemoglobin called? | What are its subunits?

Answer 52

Hb F | 2 alpha, 2 gamma