Hemoglobin

Question 1

How many red blood cells are produced per second?

Answer 1

2.4 million RBC/s

Question 2

How long do red blood cells last?

Answer 2

120 days

Question 3

What is the function of erythrocytes?

Answer 3

To transport oxygen from the lungs to the tissue.

Question 4

How man liters of O₂ per day do human red blood cells carry?

Answer 4

500-1,000 liters

Question 5

What percent volume of the erythrocyte does hemoglobin occupy?

Answer 5

33%

Question 6

What percent of hemoglobin is synthesized before extrusion of the nucleus?

Answer 6

65%

Question 7

Reticulocytes make what remaining percent of Hb?

Answer 7

35%

Question 8

What percent of protein synthesis in reticulocytes is globin synthesis?

Answer 8

95%

Question 9

Explain the stages of erythropoiesis, what happens at each phase, and what cell types are present?

Answer 9

Stem cell: (Hemocytoblast)
Commited cell: (Proerythroblast)
Phase 1: “ribosome synthesis” (Early erythroblast, Late erythroblast)
Phase 2: “Hb accumulation” (Late erythroblast, Normoblast)
Phase 3: “nucleus ejection” (Normoblast, Reticulocyte)
: Erythrocyte

Question 10

What part of the body makes red blood cells at each point of development?

Answer 10

0-8 wks: Yolk sac
1 mos-birth: Liver
2 mos-birth+2 mos: Spleen
7 mos+: Bone marrow

Question 11

What are the hemoglobin levels by age and sex?

Answer 11

Adult male: 14-18 g/dL
Adult female: 12-16 g/dL
Newborn: 111-16 g/dL
Child: 12-15 g/dL

Question 12

What is the subunit protein structure of hemoglobin?

Answer 12

Tetramer

Question 13

What is the globin stuctrue of hemoglobin?

Answer 13

2 ∝-globin chains

2 β-globin chains

Question 14

How many heme per subunit and what is the charge of the iron atom?

Answer 14

1 heme per subunit

ferrous iron, Fe²⁺

Question 15

What kind and how many rings are in the hemoglobin structure?

Answer 15

4 protoporphyrin IX rings

Question 16

What are the types of globin chains in a normal adult?

Answer 16

∝ (alpha)
β (beta)
𝛿 (delta)
γ (gamma)

Question 17

What is the length of the globin chains?

Answer 17

∝ globin= 141 amino acids

all others= 146 amino acids

Question 18

Which chains are ∝-like?

Answer 18

ζ (zeta)

∝ (alpha)

Question 19

Which chains are β-like?

Answer 19

ε (epsilon)
γ (gamma)
𝛿 (delta)
β (beta)

Question 20

What are the globin genes?

Answer 20

HBA1, HBA2, HBB

Question 21

What are the homoglobin names?

Answer 21

HbA, HbS, HbSC, HbF, Gower, Portland

Question 22

Where are the globin genes located?

Answer 22

β globin genes= Chromosome 11

∝ globin genes= Chromosome 16

Question 23

When is embryonic hemoglobin expressed and where is it made?

Answer 23

Yolk sac from 0-8 wks

Question 24

When is fetal hemoglobin primarily expressed and where is it predominately made?

Answer 24

Liver & bone marrow from 34-36 wks

Question 25

What does hemoglobin switching depend on?

Answer 25

Gestational age (time of fertilization)

Question 26

What percentage of each hemoglobin type is present in a normal adult?

Answer 26

HbA: 97%
HbA2: 3%
HbF: 0.5%

Question 27

What are the different types of hemoglobin and what globin chains are they made of?

Answer 27

Adult:
*HbA (∝2β2)
*HbA2 (∝2𝛿2)
Fetal:
*HbF (∝2γ2)
Embryonic:
*Hb Gower 1 (ζ2ε2)
*Hb Gower 2 (∝2ε2)
*Hb Portland (ε2γ2)
Sickle cell:
*HbS

Question 28

What substitution occurs to cause sickle cell anemia and at what position does it occur?

Answer 28

An amino acid at position #6 in β globin substitutes valine for glutamic acid.

Question 29

What causes the sickle shape shape in sickle cell anemia?

Answer 29

Polymerization of hemoglobin forming rods?

Question 30

What are symptoms associated with sickle cell anemia?

Answer 30

Impeded circulation, hemolytic anemia, pain, organ damage strokes increased infections

Question 31

What is a treatment for sickle cell anemia and what is the drawback?

Answer 31

Treatment with hydroxyurea to induce HbF & address inflammation. It is a chemotherapeutic agent.that can cause cancer.

Question 32

In what order are globin genes arranged on the chromosome?

Answer 32

Linearly 5’ to 3’ in the same order of activation as expression.

Question 33

What is the prosthetic group of hemoglobin?

Answer 33

Heme, a non-amino acid group

Question 34

What is the organic component of heme and how many pyrole rings does it have?

Answer 34

Protoporphyrin

4 pyrole rings

Question 35

How are amino acids labeled in hemoglobin?

Answer 35

Names according to helical segment & # amino acid in that segment e.g. F8 & E7

Question 36

Which amino acid is bound to the heme group?

Answer 36

F8 the proximal histidine

Question 37

Which amino acid is bound to the iron that O₂ binds to along with heme?

Answer 37

E7 the distal histidine

Question 38

What stabilizes O₂ binding to iron?

Answer 38

E7 forming a H-bond with O₂

Question 39

What occurs after O₂ binds iron?

Answer 39

A 0.4 Å shift pulls the rest of the globin chain pulling the F8 histidine

Question 40

What is the structure of myoglobin?

Answer 40

Monomer

Question 41

Where and at what pressure does hemoglobin pick up O₂ and where and at what pressure does hemoglobin drop off O₂?

Answer 41

Picks up O₂ in the lungs @ 100 mm Hg and drops it off to myoglobin in the tissues @ 10-20 mm Hg

Question 42

What does it mean that O₂ binds cooperatively and what kind of curve represents this?

Answer 42

1 O₂ binding causes conformational ∆ in ∝-helix which ↑ affinity to bind more O₂. Represented by sigmoidal curve

Question 43

What modulates Hb function and how does it change O₂ affinity?

Answer 43

↑ 2,3-BPG= ↑T form= ↓ O₂ affinity
↓ pH= ↓O₂ affinity
R form= ↑O₂ affinity

Question 44

What is the sequential model?

Answer 44

Hb binds/releases O₂ sequentially

Question 45

What is the concerted model?

Answer 45

Hb binds/releases O₂ all at once

Question 46

What is carboxyhemoglobin and how strongly does it bond O₂?

Answer 46

CO+heme→carboxyhemoglobin, CO bond= 210* O₂ bond

Question 47

What is HbA1c? What is its normal level and diabetic level?

Answer 47

β-globin+glucose→ HbA1c= irreversible.

Normal level= 3%= 2-3 in diabetics