L.4 Structure & Function of Haemoglobin

Question 1

What type of molecule is O2?

Answer 1

Nonpolar molecule

Question 2

How does Hb affect O2 solubility in blood?

Answer 2

Increases O2 solubility by about 100 fold

Question 3

What would happen without Hb in terms of blood circulation?

Answer 3

Blood would have to make a complete circuit in less than a second

Question 4

What percentage of a red cell’s dry weight does Hb constitute?

Answer 4

About 95%

Question 5

At what stage does Hb synthesis start?

Answer 5

Pro-erythroblast stage

Question 6

What percentage of Hb synthesis occurs during the nucleated stages of RBC maturation?

Answer 6

65%

Question 7

What percentage of Hb synthesis occurs during the reticulocyte stage?

Answer 7

35%

Question 8

Where is haem produced in maturing cells?

Answer 8

In mitochondria and cytosol

Question 9

Where is globin produced in maturing cells?

Answer 9

In cytosol by ribosomes

Question 10

What is Hb?

Answer 10

A conjugated globular protein

Question 11

What are the components of Hb?

Answer 11

Globin and four haem groups

Question 12

What is the structure of globin in Hb?

Answer 12

A tetramer of two parts of unlike globin polypeptide chains

Question 13

What is each haem group composed of?

Answer 13

A protoporphyrin ring with an iron atom in the center

Question 14

How many different types of haemoglobin do adult RBCs have?

Answer 14

Three different types

Question 15

What is the composition of HbA?

Answer 15

α2β2

Question 16

What percentage of adult hemoglobin is HbA?

Answer 16

96-98%

Question 17

What is the composition of HbA2?

Answer 17

α2δ2

Question 18

What percentage of adult hemoglobin is HbA2?

Answer 18

1.5-3.2%

Question 19

What is the composition of HbF?

Answer 19

α2γ2

Question 20

What percentage of adult hemoglobin is HbF?

Answer 20

0.5-0.8%

Question 21

What is the primary function of myoglobin?

Answer 21

Oxygen-carrying protein of the muscle

Myoglobin is particularly abundant in the muscles of diving mammals, allowing them to use oxygen underwater.

Question 22

In which animals is myoglobin particularly abundant?

Answer 22

Diving mammals, like seals and whales

Myoglobin allows these animals to continue using oxygen during prolonged underwater periods.

Question 23

How many polypeptide chains does hemoglobin contain?

Answer 23

Four polypeptide chains

In contrast, myoglobin has only one polypeptide chain.

Question 24

What additional group do both hemoglobin and myoglobin contain for oxygen binding?

Answer 24

Iron-containing group (haem)

None of the amino acids in these proteins are well suited to bind oxygen alone.

Question 25

What is the significance of the switch from fetal to adult hemoglobin?

Answer 25

Occurs 3 - 6 months after birth ## Footnote This transition is crucial for adapting to breathing air after birth.

Question 26

How many haem groups are present in each hemoglobin molecule?

Answer 26

Four haem groups ## Footnote Each haem group contains a porphyrin ring with Fe++.

Question 27

Where is haem synthesized?

Answer 27

In the mitochondria and cytoplasm of the developing normoblast ## Footnote This synthesis is essential for proper hemoglobin function.

Question 28

What is the relationship between the rates of globin synthesis and haem synthesis?

Answer 28

1:1 ratio ## Footnote The rate of globin synthesis matches the rate of haem synthesis.

Question 29

What is the role of pyridoxal phosphate (vitamin B6) in haem synthesis?

Answer 29

Acts as a coenzyme for the reaction ## Footnote This reaction is stimulated by EPO.

Question 30

What is the first step in haem synthesis?

Answer 30

Condensation of glycine and succinyl coenzyme A ## Footnote This process is catalyzed by the key rate-limiting enzyme δ-aminolaevulinic acid (ALA) synthase.

Question 31

What ultimately combines with iron to form haem?

Answer 31

Protoporphyrin ## Footnote Each haem molecule then combines with a globin chain.

Question 32

What forms a tetramer of hemoglobin?

Answer 32

Four globin chains each with its own haem group ## Footnote This structure is crucial for the function of hemoglobin.

Question 33

What is the genetic control of globin synthesis?

Answer 33

Each globin is under separate genetic control

Question 34

Where is the α gene cluster located?

Answer 34

On the short arm of chromosome 16

Question 35

How many functional α gene loci are present on each chromosome 16?

Answer 35

2 functional α gene loci

Question 36

What proportion of the gene product is produced by α1 and α2?

Answer 36

α1 is responsible for 1/3 and α2 for 2/3 of the gene product

Question 37

What is the length of the α chain produced by the α gene?

Answer 37

141 amino acids

Question 38

On which chromosome is the β gene locus located?

Answer 38

Chromosome 11

Question 39

What is the length of the β chain produced by the β gene?

Answer 39

146 amino acids

Question 40

In normal circumstances, what is the ratio of the product of the α and β, δ, and γ genes?

Answer 40

1:1 ratio

Question 41

Where are the main sites of protoporphyrin synthesis in the developing red cell?

Answer 41

Mitochondria

Question 42

From where is iron (Fe) supplied for globin synthesis?

Answer 42

From circulating transferrin

Question 43

Where are globin chains synthesized?

Answer 43

On ribosomes

Question 44

How is haem oxygenated in the lungs?

Answer 44

Due to its structure and the difference in partial pressure between the lung and the portal system

Question 45

How does oxygen cross the thin layer of epithelial cells?

Answer 45

By simple diffusion

Question 46

What happens to haem as it takes on O2 at the lungs?

Answer 46

It causes a conformational change, allowing the second haem molecule to be oxygenated

Question 47

What is the term for the phenomenon where subsequent haem molecule oxygenation occurs easier?

Answer 47

Haem-Haem interaction

Question 48

What is the oxygen saturation of hemoglobin at the lung?

Answer 48

96% saturated

Question 49

What type of movement does hemoglobin exhibit as it binds and releases O2?

Answer 49

Allosteric movement

Question 50

What does hemoglobin carry from the lungs to the tissues?

Answer 50

O2

Question 51

What does venous blood return to the lungs?

Answer 51

CO2

Question 52

What effect does pH and CO2 concentration have on hemoglobin's affinity for oxygen?

Answer 52

This is known as the Bohr effect

Question 53

What occurs to the β-chains of hemoglobin when it is in its deoxygenated state?

Answer 53

They are slightly separated, allowing 2,3-diphosphoglycerate (2,3-DPG) to enter the Hb molecule

Question 54

What happens to 2,3-DPG when hemoglobin is in its oxygenated state?

Answer 54

It is ejected

Question 55

What is 2,3-Diphosphoglycerate (2,3-DPG)?

Answer 55

An organic phosphate that controls hemoglobin (Hb) affinity for oxygen

Question 56

What is the source of 2,3-DPG?

Answer 56

It is derived from anaerobic glycolysis

Question 57

What is the primary role of 2,3-DPG in the body?

Answer 57

Regulates Hb-O2 release

Question 58

How does increased 2,3-DPG affect oxygen release?

Answer 58

Increases O2 release

Question 59

Where is 2,3-DPG located in the hemoglobin molecule?

Answer 59

In the central cavity of Hb

Question 60

To which part of hemoglobin is 2,3-DPG bound?

Answer 60

Beta chains

Question 61

What is the function of hemoglobin in relation to oxygen and carbon dioxide?

Answer 61

Delivery and release of oxygen to tissues and facilitation of carbon dioxide excretion

Question 62

What does the Oxygen Dissociation Curve represent?

Answer 62

Plots Hb saturation against prevailing oxygen tension

Question 63

What is the P50 value?

Answer 63

The partial pressure of oxygen at 50% saturation

Question 64

What is the normal P50 value?

Answer 64

26.6 mmHg

Question 65

What effect does an increase in CO2 have on the oxygen dissociation curve?

Answer 65

Decreases O2 affinity of Hb, shifting the curve to the right

Question 66

What generates hydrogen (H+) ions in the blood?

Answer 66

CO2 reacting with water

Question 67

What conditions decrease O2 affinity of hemoglobin?

Answer 67

* Sickle cell anemia * Increased body temperature * Increased CO2 levels

Question 68

What effect does decreased 2,3-DPG levels have on O2 affinity?

Answer 68

Increases O2 affinity, making O2 given up less readily

Question 69

How does the O2 affinity of HbF compare to HbA?

Answer 69

HbF has a higher affinity for O2 than HbA

Question 70

Why does HbF have a higher affinity for oxygen?

Answer 70

γ-chains bind to 2,3-DPG more weakly than β-chains

Question 71

What is the significance of HbF's high affinity for oxygen?

Answer 71

Facilitates O2 transport from mother to fetus