Erythrocyte Biochemistry Flashcards

1
Q

What makes R-Binder proteins?

A

Gastric mucosa cells in the stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where does nonheme iron come from?

A

Plant products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Oxygen Dissociation curve for hemoglubin

A

Sigmoidal curve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The uptake of transferin by cells is done by what process?

A

Receptor mediated endocytosis via transferin receptor (TfR).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

B12 deficiency is often caused by what.

What impact can this deficiency have?

A

Dietary lack is not often the cause, 3 ug dailly allowance

85% of cases are the lack of a protein called intrinsic factor.

Causes megaloblastic anemia because of the decrease of N5,10-methylene-THF and on DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the efficiency of hemoglobin in delivery of oxygen to from lung to tissue.

A

Drops from 7.4 to 7.2 pH

66%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe B12 Absorbtion

A

B12 binds to R-binder proteins in somach

Degraded by proteases in the dudenom releasing B12

Intrinsic factor carries B12 to ileum where it is absorped by receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In what form foes ferritin store iron?

A

As Fe3+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What converts Fe3+ in non-heme iron to Fe2+

A

Ferric Reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the generation of erythrocytes known as?

A

Erthropoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where does heme iron come from?

A

Animal products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why is HbF in the fetus higher in affinity the HbA in the mother?

A

Oxygen travels mother to fetus.

HbF does not bind well to 2,3-BPG so this cannot decrease its affinity as much.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens to affininty for oxygen as pH decreases. How does this work and what is this effect called?

A

O2 affinity decreases as pH decreases

His 146 picks up H+ from tissue and causes a conformational change in Hg.

Called the Bohr Effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do internalized endosomes get transferin to the mitchondira for heme synthesis?

A

Clatherin coated endosome transiently docks and DMT1 helps to facilitate the transport of iron out of the endosome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

2,3-Biphosphoglycerate has what effect on O2?

A

Reduces the affinity of O2 so Hb gives up more O2 to tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What form of folate is dietary?

A

Dihydrofolate (DHF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is portential therapy for sickle cell anemia?

What are the worries in this?

A

Changing HbS to HbF using hydroxyurea

This is a toxic chemotherapeutic agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What cell features are observed in megaloblastic anemia?

A

Large erythrocytes >100 fL (normal is 80-100) (same ratio of hematocrit)

Large erythroblasts

Hyper-segmented neutrofills (more then 5 lobes, 3-4 normal)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is B12 transported into and throughout the blood

A

Intrinsic factor bound to cobalin is taken up by receptor-mediated endocytosis.

Cobalin circulates through the blood by transcobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Stem cells and commited cells of erthropoiesis

A

Hemocytoblast

Proerythroblast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What can result as part of Hereditary Hemochromatosis?

A

Organ dysfunction due to iron overload: cirrhosis, arthritis, endocrinopathy, skin pigmentation, cardiomyopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the function of THF?

A

Transfers carbon units from donors to acceptors

Is vital for DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What transports iron in the blood?

A

Transferrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What enzyme refuces folate to DHF and THF?

A

Dihydrofolate reductase

Oxidizes NADPH to NADP

Add 2 electons + hydrogens at a time

25
Q

Describe folate metabolism.

A

THF to N5,10-methylene-THF as the carbone side chain of a serine is transfered

Carbon of N5,10-methylene-THF is transfered to deoxyuridylate (dUMP) to form deoxythmidylate (dTMP) during which DHF is made

26
Q

How does positive cooperativity work?

A

The binding of O2 to Fe of a globin subunit pulls the proximal F8 histindine down ==> this pulls the globin FG-helix and changes the interaction with the other globin chain in Hb

27
Q

What converts free iron to Fe3+?

A

Hephaestin/cerruplasmin

28
Q

Dysregulation of iron uptake and export by enterocyte

15g of Total iron body weight

What is the disease and treatment?

A

Hereditary Hemochromatosis

Blood letting

29
Q

What is the fetal hemoglubin and when does it peak?

A

Hb F (a2g2)

Gamma chain peaks right before birth and then subsides.

Alpha continually increases up untill birth where it levels off.

30
Q

What makes Intrinsic factor?

A

Pariatal cells in the stomach.

31
Q

How does regulation of hepciden work?

A

Tf-Fe bind s Tfr1

This causes Hfe to bind to Tfe2

Tf2 then upregulats signal transduction of hepcidin

32
Q

What takes up Fe2+ in the enterocyte.

A

Divalent transporter-1 (DMT1)

33
Q

What percentage of Iron is stored and in what forms?

A

27%

Ferritin and hemosiderin

34
Q

What takes Fe 2+ out of the cell?

A

Ferroportin

35
Q

How is pernacious anemia tested?

A

Serum folate <3 ng/ml

Serum B12 <350pg/ml

Coduct Schilling Test

36
Q

Distal hisitidine location. What does it stabilize binding of?

A

E7 binds to the iron between the heme and distal histidine

Binds with oxygen.

37
Q

How does the comformation of hemoglubin change when oxygen bind?

A

A 0.4 Å change pulls down the proximal F8 histidine of Hb and
changes interaction with associated globin chain

38
Q

What would a mutation in Hfe cause?

A

Hemotomachromatosis

Can no longer bind to Tf2 and cause upregulation of hepcidin, therefore it would lead to overload of iron in blood

39
Q

Oxygen Dissociation curve for Myoglubin

A

Hyperbolic curve

40
Q

Why is cobalamin essential to overcoming the folate trap?

A

Vitamin B12 removes a methyl group from N5-methyl-THF to make methyl-cobalalmin (B12-CH3) and THF

41
Q

How do you conduct the Schilling test?

A
  1. 5-1.0 ug oral dos of 57Co-labled B12 (simultaneously saturating all cobalim receptor s with 1,000ug injection of B12).
  2. If radioactive urine after 24 hours = healthy and diet is the problem (STOP)
  3. If not radioactive urine after 24 hours = pernacious anemia

(GO ON TO 3.)

  1. Repeat with B12 doses given with Intrinsic factor, if radioactive its due to a lack of intrinsic factor.
42
Q

What are the adult hemogblubins

A

Hb A (a2b2) 97%

Hb A2 (a2g2) 3%

Beta increases more rapidly after birth and to a greater degree then gamma

43
Q

What are the embryonic hemeglobins and when are they gone?

A

Hb Gower 1

Hn Gower 2

Hb Portland

44
Q

What are the tetramer chains in Hemoglubin

A

2 alpha-globin chains

2 beta-globin chains

45
Q

What is added to THF to create a C-FH4 donor?

A

Addition of CH2

46
Q

Where is folate absorbed and where is it absorbed?

A

The jejunum

Liver stores 5 to 10 mg folate which can last 2 to 6 months

47
Q

Peptide that binds to ferroportin causing internalization and proteolysis of ferroportin.

Explain it’s regulation of iron homeostasis

A

Hepcidin

Iron High = Hepcidin Up = Ferroportin Down

48
Q

Steps of the developmental pathway in erythropoeisis.

A

Early erythroblast -> Late erythroblast (Ribosome synthesis)

Late erythroblast -> Normoblast (Hemeoglubin accumulation)

Normoblast -> Retulocytes (Ejection of nucleus)

Retulocytes -> Erythrocytes

49
Q

What does hepcidin overexpression result in?

What about underexpression?

A

Low plasma iron levels

Overloaded plasma iron levels.

50
Q

What causes hypochromic microcytic anemia?

A

Iron Defieciency

Insufficient dietary iron

Menstration

Aspirin overuse

Ulcers of GI tract (Blood loss)

Treatment - dietary iron supplementation

51
Q

Why is B12 needed in folate acid metabolism?

A

N5-methyl-THF requires cobalamin to transfer a single methylene group to dUMP to make dTMP (for DNA synthesis)

Stuck as N5-methyl-THF known as the folate trap

52
Q

Where is the proximal hisitidine located at?

A

F8 Histidine bound to heme

53
Q

What can HbS cause in hemoglubin?

A

Polymerization

54
Q

Why is methene-THF important and what does it do?

A

Synthesis of nucleotides through addition of methylene

THF grabs methyl groups using 2 Nitrogens

55
Q

What reduces Fe3+ to Fe2+ on cell surface?

A

Dcytb (duodenal cytochrome b) aka Ferric Reductase

56
Q

What is a healthy iron body weight

A

3 to 5g

57
Q

What is pernacious anemia

A

Lack of intrinsic factor results in megaloblastic macrocytic anemia due to lack of B12.

Results in:

Gastric mucosa destroyed through auto-immune mechanism Decreased intrinsic factor

58
Q

How does RBC production depend of folate and B12

A

It does so for DNA synthesis.

If there is a decrease in this it can result in megaloblastic anemia.