Lecture 6: Erythrocyte Biochemistry Flashcards Preview

Year 1: 09. CPR Exam 2 > Lecture 6: Erythrocyte Biochemistry > Flashcards

Flashcards in Lecture 6: Erythrocyte Biochemistry Deck (39)
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1
Q

How does the structure of hemoglobin differ between adult and fetal forms?

A

Adult: 2 alpha and 2 beta globin chains
Fetal: 2 alpha and 2 gamma globin chains

2
Q

What state is the iron atom in a heme?

A

Fe 2+ (ferrous)

3
Q

When oxygen binds to a heme group, what happens to iron ion?

A

Iron movies into plane of heme and pulls down the proximal histidine of hemoglobin
-oxygen forms a hydrogen bond with histidine

4
Q

What type of oxygen saturation curve is seen with a myoglobin?

A

Hyperbolic curve

-only 1 peptide

5
Q

What type of oxygen saturation curve is seen with a hemoglobin?

A

Sigmoidal curve

-due to interaction between four globin subunits

6
Q

Describe positive cooperativity.

A

The binding of one oxygen molecule to hemoglobin makes it easier to bind to other oxygen molecules
-change in one globulin subunit induces a change in another subunit

7
Q

What is the Bohr Effect?

A

Decreased affinity of hemoglobin for oxygen

-releases oxygen (want this in tissues)

8
Q

What changes are seen in Bohr Effect?

A

1) Decrease in pH (increase in H+)
2) Increase in 2,3-BPG (tells Hb to give up oxygen)
3) Exercise (drop in partial pressure of oxygen)

9
Q

Why is affinity for oxygen higher in fetal red cells compared to maternal red cells?

A

Fetus needs to get oxygen from mother

  • fetal Hb does not bind well to 2,3-BPG
  • left shift
10
Q

In sickle cell disease, where is the mutation?

A

Amino Acid position #6 in beta globulin

  • glutamic acid changes to valine
  • polymerization of hemoglobin
11
Q

Where is iron stored?

A
  • Cells that line intestine
  • Liver
  • Spleen
  • Bone Marrow
12
Q

How is heme iron stored?

A

1) Fe 2+ (heme) enters enterocyte (intestinal cell) and converted into Fe 3+ via ferroxidase
2) Stored as ferritin and can be degraded into hemosiderin

13
Q

How is non-heme iron stored?

A

1) Fe 3+ is converted into Fe 2+ in the intestinal lumen via ferric reductase in presence of Vit C
2) Fe 2+ enters enterocyte via DMT1
3) Fe 2+ is converted into Fe 3+ via ferroxidase
4) Stored as ferritin and can be degraded into hemosiderin

14
Q

How does iron leave the enterocyte?

A

1) Must be in Fe 2+ state
2) Leaves basolateral side via ferroportin.
3) Converted to Fe 3+ via ferroxidase
4) Transferrin transports Fe 3+ to liver, spleen, bone marrow

15
Q

Ferroportin requires what for its function?

A

Hephaestin

16
Q

Ferroportin levels and iron content in the body are regulated by?

A

Hepcidin

17
Q

Describe the process of transferrin uptake.

A

1) Uptake via receptor-mediated endocytosis via transferrin receptor
2) Internalized via clathrin pits
3) Transferrin is released in endosome due to low pH
4) Iron is uptaken in mitochondria via DMT1

18
Q

What happens when hepcidin binds to ferroportin?

A

Internalization of ferroportin and subsequent degradation in lysosomes

19
Q

What regulates levels of hepcidin?

A

Transferrin and its receptor: Human homeostatic iron regulator protein (HFE)

  • High levels of iron (transferrin)n–> hepcidin expression up –> low levels of ferroportin –> low iron absorption levels
  • Low levels of iron (transferrin) –> hepcidin expression down –> high levels of ferroportin –> high iron absorption levels
20
Q

What can cause iron deficiency?

A
  • Insufficient dietary iron
  • Insufficient absorption
  • Excessive blood loss via menstruation
  • Overuse of aspirin
  • Ulcers of GI tract
21
Q

What can iron deficiency cause?

A

Hypochromic microcytic anemia

22
Q

What can iron overload cause?

A

Hereditary Hemochromatosis

  • accumulation of iron in heart, liver, and pancreas, which can cause severe issues
  • autosomal recessive in HFE gene
  • 15 g of iron instead of normal 3-5
23
Q

RBC production is dependent on what?

A
Folate
Vitamin B12 (cobalamin)
24
Q

What can a deficiency in folate and vitamin B12 cause?

A

Megaloblastic anemia

  • diminished synthesis of DNA
  • large RBC
25
Q

What is the active form of folate?

A

Tetrahydrofolate (THF)

26
Q

What is the role of THF?

A

Synthesis of purines and thymine

27
Q

Where is folic acid absorbed?

A

Small intestine (jejunum)

28
Q

Where is folic stored?

A

Liver

29
Q

In dietary sources, folate is in what form?

A

DHF

30
Q

In the intestines, folate acid is reduced to what form?

A

N5-methyl-THF

31
Q

What enzyme converts FH2 (DHF) into FH4 (THF)

A

Dihydrofolate Reductase

32
Q

What inhibits dihydrofolate reductase?

A

Methotrexate

33
Q

What is an important component of Vit B12?

A

Cobalt

34
Q

What does Vit B12 do?

A

Removes methyl group from N5-methyl-THF to generate FH4 (THF)

35
Q

Where is Vit B12 found?

A

Animal products

-made by microorganisms

36
Q

What is the main cause of Vit B12 deficiency?

A

Lack of protein: intrinsic factor

37
Q

How is Vit B12 absorbed?

A
  1. Dietary Vit B12 binds to R-binder proteins
  2. Intrinsic factor carries B12 to ileum and it is released into blood stream from there by transcobalamin II
  3. Intrinsic Factor-cobalamin complex taken up by cells via receptor-mediated endocytosis
38
Q

What is pernicious anemia?

A

Megaloblastic macrocytic anemia

-Vit B12 deficiency due to lack of intrinsic factor

39
Q

How do you test for pernicious anemia?

A

1) Oral dose radioactive Vit B12
- if it is seen in urine 24 hours later, then it has been absorbed

2) If radioactive Vit B12 not seen in urine, oral dose of radioactive Vit B12 + Intrinsic factor
- if it is seen in urine 24 hours later, then pernicious anemia is due to lack of intrinsic factor