Haemoglobin Structure & Function

Question 1

When does globin synthesis begin?

Answer 1

Globin synthesis starts from the third week of gestation (prenatal) in the yolk sac

Question 2

What does a decrease in O2 affinity cause?

Answer 2

Causes oxygen release

Question 3

What is the result of high oxygen affinity?

Answer 3

Increased O2 affinity
=> Hb has highr O2 affinity
=> binds more strongly

Question 4

What does a normal Hb curve depened on

Answer 4

[2,3-DPG]
[H+] (pH)
CO2 in RBC
Hb structure

Question 5

How are different forms of Hb formed?

Answer 5

Various types of globin combine with haem to form the different haemoglobin
8 functional globin chains arrange in 2 clusters (A and B)

Question 6

Describe the Bohr effect on oxyhaemoglobin curves

Answer 6

1. An increase in CO2 production by tissues
2. CO2 released into blood
3. Dissociation curve shifts to right
4. Release of O2 from Hb diffuses into tissues
   - lower O2 affinity = unloaded readily

Question 7

Describe the structure of Hb

Answer 7

• Globin chains have 4 polypeptide subunits (tetramers)
• 2 α globin chains
• 2 β globin chains
  Each globin chain contains its own haem

Question 8

What does a Bohr curve shifted to the right indicate?

Answer 8

Shift right = low affinity for O2
e.g.
Anemia, acedosis
despite less RBCs, they act more efficiently to deliver o2 to their target tissues

Question 9

Outline the steps of O2 binding and unloading

Answer 9

1. β chains slide over each other
2. When oxygenated the globin chains move closer
3. Deoxygenated globin chains pulled apart for 2,3-DPG -
   decreasing affinity

Question 10

Outline the significance of Globin?

Answer 10

In polyribosomes

• depends on genes
• precise order of amino acids in globin chains determines the function of Hb

Question 11

What are the factors determining how much O2 binds to Hb?

Answer 11

• PO2
• PCO2
• Hb affinity for O2

Question 12

What is oxygen affinity?

Answer 12

Ease with which haemoglobin binds and releases oxygen

Determines proportion of O2 released to tissues or loaded onto cells at a given oxygen pressure

Question 13

What is indicated by a Bohr curve shifted to the left?

Answer 13

Left shift = high O2 affinity
e.g.
Presence of abnormal Hb, alkalosis
Hb less readily unloads O2 to tissues, binds strongly

Question 14

What is the consequence of mutations on haemoglobin?

Answer 14

Deletions/mutations may lead to

• abnormal globin synthesis (sickle cell)
• Reduced rate of globin synthesis (thalassemia)

Question 15

What is the relationship between 2,3-DPG and Oxygen delivery?

Answer 15

Increased 2,3-DPG causes more oxygen delivery to tissues

This is the body’s main response to hypoxia

Question 16

What are the functions of Hb?

Answer 16

Carry O2 from lungs to tissues

• Remove CO2
• Buffer (maintains blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin

Question 17

How is Haem synthesised?

Answer 17

In mitochondria
1. Iron supplied to reticulocyte by transferrin enzyme
2. Protoporphyrins (RBC precursors) synthesised (via EPO
and Vit. B12 regulation)
3. Protoporphyrin + Iron => Haem

Question 18

How is CO2 transported in the body?

Answer 18

There are 3 mechanisms for CO2 transport

1. Dissolution in plasma
2. Formation of Carbonic acid
3. Binding to carbaminohaemoglobin

Question 19

What is 2,3-DPG?

Answer 19

2,3-diphosphoglycerate is a metabolite formed in red blood cells
controls the movement of oxygen from RBCs to tissues

Question 20

How is Hb production regulated?

Answer 20

Regulation stimulated by hypoxia

Causes kidneys to produce more EPO, increasing RBC and Hb production

Question 21

How does Hb transport oxygen?

Answer 21

1 Hb can bind to 4 oxygen in <0.01s
When oxygenated 2,3-DPG pushed out
β chains move closer together

Question 22

How is Oxygen unloaded to tissues?

Answer 22

β chains pulled apart
2,3-DPG can enter between chains
results in lower O2 affinity

(this is responsible for the sigmoidal shape of oxygen dissociation curves)

Question 23

What is the normal [Hb] in blood?

Answer 23

Adult male: 13.5-16.5g/dl

Adult femaile: 12.5-15.0g/dl

Question 24

Which red cell precursors does Hb synthesis occur in?

Answer 24

65% in erythroblasts

35% in reticulocytes

Question 25

How are the components of Haemoglobin synthesised in accordance to one another to produce sufficient Hb?

Answer 25

Haem and globin synthesis occur separately in developing red cell precursors
Synthesis rates are carefully coordinated to ensure optimal efficiency of Hb assembly