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HEMATOLOGY > 5. HEMOGLOBIN PART 1 > Flashcards

5. HEMOGLOBIN PART 1 Flashcards

1
Q

What is the approximate concentration of hemoglobin in red blood cells (RBCs)?

A

34 g/dL

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2
Q

What percentage of the cytoplasmic content of RBCs is hemoglobin?

A

95%

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3
Q

What is the molecular weight (MW) of hemoglobin?

A

64,000 Daltons

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4
Q

List the main functions of hemoglobin.

A

Transports oxygen, carbon dioxide, nitric oxide, and

contributes to acid-base balance.

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5
Q

What is the structure of heme in hemoglobin?

A

Protoporphyrin IX (a ring of carbon, hydrogen, and nitrogen atoms) + Ferrous iron (Fe2+)

Ferroprotoporphyrin IX

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6
Q

How many oxygen molecules can one heme group bind to?

A

One O2 molecule

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6
Q

What does each globin structure in hemoglobin consist of?

A

Two identical pairs of unlike polypeptide chains.

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7
Q

What happens when Fe2+ in heme is oxidized to Fe3+?

A

It forms Methemoglobin, which is non-functional and cannot carry oxygen.

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8
Q

How is a single globin chain structured?

A

A globin chain has 8 helices (linear and rigid) separated by 7 nonhelical segments (flexible).

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8
Q

How does variation in globin chains affect hemoglobin?

A

Variation in amino acid sequences of globin chains gives rise to different types of hemoglobin.

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9
Q

How many amino acids are present in the alpha (α) globin chain?

A

141

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10
Q

Which chromosome contains the alpha (α) globin chain gene?

A

Chromosome 16

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11
Q

How many amino acids are present in the beta (β) globin chain?

A

146

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12
Q

Which chromosome contains the beta (β) globin chain gene?

A

Chromosome 11

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13
Q

How many amino acids are present in the gamma (γ) globin chain?

A

146

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14
Q

Which chromosome contains the gamma (γ) globin chain gene?

A

Chromosome 11

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15
Q

How many amino acids are present in the delta (δ) globin chain?

A

146

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16
Q

Which chromosome contains the delta (δ) globin chain gene?

A

Chromosome 11

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17
Q

How many amino acids are present in the epsilon (ε) globin chain?

A

146

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18
Q

Which chromosome contains the epsilon (ε) globin chain gene?

A

Chromosome 11

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19
Q

How many amino acids are present in the zeta (ζ) globin chain?

A

141

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20
Q

Which chromosome contains the zeta (ζ) globin chain gene?

A

Chromosome 16

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21
Q

What is HbA1c, and what percentage is normal?

A

Glycated hemoglobin, 4% to 6%

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21
Q

The predominant adult hemoglobin

A

Hb A

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21
Q

What does 1 hemoglobin (Hb) molecule consist of?

A

4 heme + 4 globin chains

21
Q

What are the four structural levels of a hemoglobin molecule?

A

Primary: Amino acid sequence

Secondary: Helices and nonhelices

Tertiary: Pretzel-like helix arrangement with heme between E & F helices

Quaternary: Tetramer, 4 heme + 4 globin, spherical

21
Q

What is the composition of 1 heme molecule?

A

4 pyrrole rings + 1 iron (Fe²⁺)

21
Q

How much oxygen can one hemoglobin (Hb) molecule carry?

A

4 moles of O₂ (1 Hb = 4 heme, each heme = 1 O₂)

21
Q

Where does hemoglobin synthesis occur?

A

In the mitochondria and cytoplasm of bone marrow erythroid precursor cells

22
Q

At what stages does hemoglobin synthesis begin and end?

A

Begins: Basophilic normoblast (prorubricyte)
Ends: Polychromatophilic erythrocyte

23
Q

What are the key steps of heme synthesis?

A
  1. Glycine + Succinyl CoA → ALA (in mitochondria)
  2. ALA → porphobilinogen → coproporphyrinogen III (in cytoplasm)
  3. Coproporphyrinogen III → Protoporphyrin IX + Fe²⁺ = Heme (in mitochondria)
24
Q

How does iron enter the RBC precursor cell?

A

1.Transferrin with Fe³⁺ binds to receptors

  1. Taken into the endosome
  2. Acidification releases Fe³⁺
  3. Fe³⁺ enters mitochondria, reduced to Fe²⁺
25
Q

Excess protoporphyrin in the mitochondria

A

free erythrocyte protoporphyrin (FEP)?

26
Q

What happens when iron is deficient during heme synthesis?

A

FEP complexes with zinc, forming zinc protoporphyrin (ZPP)

27
Q

Where does globin synthesis occur, and what is the process?

A

In erythroid precursors:
1. Transcription in the nucleus → mRNA

  1. Translation by ribosomes → globin chains
  2. Polypeptide chains released into cytoplasm
28
Q

How does hemoglobin assembly occur?

A

Globin binds to heme

Non-α + α chains form heterodimers

Two heterodimers combine to form a tetramer

29
Q

What are the major hemoglobin types in 1st 3 months of embryonic development

A

Gower I, Gower II, Portland

30
Q

What are the major hemoglobin types in 2nd/3rd trimesters & at birth

A

Hb F predominates

31
Q

What are the major hemoglobin types in 6 months to adulthood

A

Hb A predominates

32
Q

What percentage of Hb F is found in healthy adults?

A

1%-2%

33
Q

What are the primary hemoglobins and their proportions at birth?

A

Hb F (60-90%) | Hb A (10-40%)

34
Q

What are the primary hemoglobins and their proportions in adults?

A

Hb A1 (>95%) | Hb A2 (<3.5%) | Hb F (1-2%)

35
Q

What is the key regulator of heme production?

A

Condensation of glycine & succinyl CoA to form ALA by ALA synthase

36
Q

How does heme regulate ALA synthase production?

A

Heme inhibits transcription of the ALA synthase gene, reducing heme production.

37
Q

What primarily controls globin production?

A

Globin production is mainly controlled at the transcription level.

38
Q

What are the key factors required for globin gene transcription?

A

1) Promoter DNA sequences

2) Krüppel-like factor 1 (KLF1)

3) Other transcription factors (e.g., GATA1, TAL1, p45-NF-E2)

4) Locus control region (LCR)

39
Q

What role does heme play in globin regulation?

A

Sufficient heme activates translation of initiation factor and inactivates its repressors.

40
Q

What happens when there is sufficient heme?

A

Decreases ALA synthase synthesis and activates globin mRNA translation.

41
Q

What is the globin chain composition of Gower 1 and its stage of life?

A

2 zeta, 2 epsilon | Embryonic

42
Q

What is the globin chain composition of Gower 2 and its stage of life?

A

2 alpha, 2 epsilon | Embryonic

43
Q

What is the globin chain composition of Portland and its stage of life?

A

2 zeta, 2 gamma | Embryonic

44
Q

What is the globin chain composition of Hb F and its stage of life?

A

2 alpha, 2 gamma | Newborn & Adult

45
Q

What is the globin chain composition of Hb A2 and its stage of life?

A

2 alpha, 2 delta | Newborn & Adult

46
Q

What is the globin chain composition of Hb A1 and its stage of life?

A

2 alpha, 2 beta | Newborn & Adult

47
Q

Group of disorders relating to synthetic defects

A

Thalassemia

48
Q

Group of disorders relating to structural defects

A

Hemoglobinopathies

49
Q

Hemoglobin weight in relation to total body mass

A

A little bit over 1%

50
Q

the oxygen-carrying capacity of hemoglobin is empirically determined to be

A

1.34 mL O2/g Hbg

51
Q

The heme is suspended in what helices

A

E and F

52
Q

Chromosome 16 transition

A

Zeta to Alpha

53
Q

Chromosome 11 transition

A

Epsilon
Gamma
Delta
Beta

HEMATOLOGY (10 decks)

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