EXAM #1: HEMOGLOBIN Flashcards Preview

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Flashcards in EXAM #1: HEMOGLOBIN Deck (54)
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1

What is the most abundant form of Hb in adult? What subunits does it have?

HbA

- Tetramer
- 2x alpha globins
- 2x beta globins

2

How many oxygen binding sites does Hb have?

4, one per subunit

3

What happens to oxygen binding as oxygen levels increase?

Hb binds O2 more efficiency at higher O2 concentrations b/c of cooperative binding

4

How does myoglobin's affinity for oxygen differ from Hb?

Myoglobin binds O2 with HIGH affinity at LOW oxygen concentrations

5

What is the effect of lower pH/ higher CO2/ lower O2 on oxygen binding?

Favors oxygen dissociation

6

What is the effect of higher pH/ lower CO2/ higher O2 on oxygen binding?

Favors oxygen binding

7

What is the effect of 2,3-BPG on oxygen binding?

Favors dissociation

8

What is Hb A2?

Hb with:
- 2 alpha globins
- 2 delta globins

9

What are the three Hb sub-types present in the early embryo? What are the subunits?

Hb Gower 1= 2-zeta and 2 epsilon
Hb Gower 2= 2 alpha and 2 epsilon
Hb Portland= 2 zeta and 2 gamma

10

What sub-type of Hb predominates as the embryo begins to age? What are the subunits?

Hb F= 2 alpha and 2 gamma

*****This is the major Hb of the fetus*****

11

When does an infant have a switch from predominantly Hb F to Hb A?

By 1 year old, the 98% of Hb is Hb A (vs. F in utero)

12

How does the oxygen affinity of Hb Gower 1,2, Portland, and F compare to Hb A?

V. high relative oxygen affinity

13

What is the purpose of increased oxygen affinity of the fetal and embryonic Hbs?

To "capture" oxygen diffusing from maternal circulation

14

What is the molecular basis of the higher affinity of Hb F for oxygen than Hb A?

- Histidine in B-chain
- Replaced with serine in gamma-chain

2,3-BPG binds to the Histidine in Hb A (Beta globin). Serine removes the positive charge that 2,3-BPG binds to, increasing the affinity of Hb F for oxygen.

15

What are the alpha-like globins? What chromosome are they encoded on?

Chromosome 16
- alpha
- zeta

*****Note that the pseudo genes are also encoded on chromosome 16--these cannot produce a functional protein product.*****

16

What are the beta-like globins? What chromosome are they encoded on?

Chromosome 11
- Beta
- Gamma
- Delta
- Epsilon

17

What is the control region located upstream to the alpha-like globins?

HS-40

Confers high level tissue specific expression of alpha-like globins

18

What is the control region located upstream of the beta-like globins?

LCR

Confers high level tissue specific expression of beta-like globins

19

What are hemoglobinopathies?

Disorders of hemoglobin

20

What are the two categories of hemoglobinopathies?

1) Structural variants-->Heinz bodies
2) Thalassemias

21

What is the definition of Thalassemia?

Imbalanced synthesis of alpha and beta globins i.e. reduced synthesis of one or more of the globin chains

22

What is a Heinz body?

- Unstable Hb forms unstable complexes and is oxidized to methemoglobin
- Methemoglobin form hemichrome
- Hemichrome aggregates form Heinz bodies

23

What are the three major Hb structural variants?

1) Hb S
2) Hb C
3) Hb E

24

What is Hb S?

This is the Hb variant found in Sickle cell disease

25

How does Hb S differ from Hb A?

Glutamate at position 6 in the Beta-globin gene is replaced with VALINE
- Valine is v. hydrophobic and polymerizes when deoxygenated

26

What is the difference between Sickle Cell Trait and Sickle Cell Disease?

Trait= heterozygous mutation

Disease= homozygous mutation

27

Explain how the valine substitution at position 6 contributes to the pathology of Sickle Cell Disease.

- Valine is EXPOSED in deoxygenated Hb S
- Exposed valine forms a hydrophobic patch
- Hb S has a tendency to accumulate and stack

Stacked Hb forms the "Sickle" distortion of RBCs

28

What are the negative consequences of having Sickle-shaped RBCs?

- Clog the microcirculation
- Reduced lifespan

Leads to hemolytic anemia

29

What is the agent of choice for the management of sickle cell disease?

Hydroxyurea

30

How does hydroxyura treat Sickle Cell Disease?

- Antineoplastic agent
- Increases Hb F
- Hb F promotes solubility of Hb and suppresses the sickling of cells