Haematology 2

Question 1

What are globular proteins?

Answer 1

They are spherical, compact proteins (‘spheroproteins’)
Most are water soluble, forming colloids (suspension)

Question 2

What is the shape, function, solubility (water), AA sequence, stability and examples of globular proteins?

Answer 2

Round/spherical
Functional (catalysts, transport)
Mostly soluble
Irregular
More sensitive to change in heat and pH
Haemoglobin (Hb), insulin, enzymes

Question 3

What is the shape, function, solubility (water), AA sequence, stability and examples of fibrous proteins?

Answer 3

Long and narrow
Structural (strength, support)
Mostly insoluble
Repetitive
Less sensitive to change in heat and pH
Collagen, keratin, elastin, fibrin

Question 4

Describe protein structure

Answer 4

1 degree- AA sequence
2 degree- a-helix, B-sheet, B-turn
3 degree- 3D folding, interaction with other parts of AA sequence
4 degree- interactions between different polypeptide subunits (e.g. disulphide bonds)

Question 5

What are the functions of proteins?

Answer 5

Storage of ions and molecules (e.g. myoglobin, ferritin)
Transport of ions and molecules (e.g. Hb, 5HT transporter)
Defense against pathogens (e.g. Ab, cytokines)
Muscular contraction (e.g. actin, myosin)
Extracellular matrix support (e.g. collagen)
Biological catalysts (i.e. enzymes)

Question 6

Tetrameric proteins (4 degrees)

Answer 6

Each with a haem group

Question 7

How do the subunits interact with each other?

Answer 7

Through hydrogen and ionic bonds (no disulphide bonds)

Question 8

How is oxygen transported?

Answer 8

In the RBCs by nitrogenous, iron (Fe 2+)- containing pigments- haem groups

Question 9

What are the three types of Hb in humans?

Answer 9

HbA, HbA2 and HbF

Question 10

What is HbA?

Answer 10

Major adult Hb
>97%
2 x a-chains
2 x B-chains

Question 11

What is HbA2?

Answer 11

Minor adult Hb
1-3%
2 x a-chains
2 x sigma-chains

Question 12

What is HbF?

Answer 12

Fetal Hb
2 x a-chains
2 x y-chains

Question 13

Features of myoglobin

Answer 13

Related to Hb but only found in muscle tissue (‘myo’)
- Cardiac or skeletal

Question 14

What type of protein is myoglobin?

Answer 14

Monomeric protein with higher affinity for O2
- 153 AA with a tightly-bound haem group

Question 15

What is myoglobin used for?

Answer 15

Short-term storage of O2 for muscular contractions

Question 16

O2 content, capacity & saturation

Answer 16

Content- quality of O2 in a sample- normal [O2Hb] for females is 13.5 g/dL and for males is 15.0 g/dL
Capacity- maximum quantity of O2 that can combine with Hb in a given sample
Saturation- ratio of O2 content: capacity in a given sample (%):
Saturation (%) = [O2Hb] / [O2Hb] + [HHb] x 100

Question 17

What is oxyhaemoglobin?

Answer 17

Oxyhaemoglobin (O2Hb) is formed by combining 4 x O2 with haem groups.
- Produces blood red colour
- Reversible binding of O2

Question 18

What is deoxyhaemoglobin?

Answer 18

At low [O2] O2Hb dissociates to deoxyhaemoglobin (HHb) and releases O2
- HHb is a darker deep purple

Question 19

What does partial pressures mean?

Answer 19

Oxygen and carbon dioxide concentrations are historically expressed as partial pressures

Question 20

What is partial pressures measured in?

Answer 20

Measured in kPa or mmHg

Question 21

What does it mean if there is high partial pressure of oxygen?

Answer 21

It is high in alveolar capillaries of the lungs.
Oxygen and Hb combine to form O2Hb

Question 22

What does it mean if there is low partial pressure of oxygen?

Answer 22

Oxygen dissociates from Hb and diffuses down its concentration gradient into cells via interstitial space

Question 23

How are the 4 Hb subunits held together?

Answer 23

By 8 strong ionic and many weak hydrogen bonds

Question 24

What happens when oxygen binding occurs?

Answer 24

It breaks the ionic bonds and forms new hydrogen bonds, relaxing the 4 degree protein structure

Question 25

What happens when oxygen binding occurs to a haem group in Hb?

Answer 25

It increases oxygen affinities of remaining haem groups
Positive co-operativity

Question 26

Does myoglobin have positive co-operativity?

Answer 26

Has one globular chain, so there is no positive co-operativity

Question 27

How many globular chains does haemoglobin have and does it have positive-cooperatively?

Answer 27

4 globular chains and positive co-operativity

Question 28

Describe the oxygen saturation curve

Answer 28

Hb is oxygenated in the capillary bed of alveoli at approximately 100 mmHg
ppO2 air is approximately 150mmHg due to competition from blood
P50 is the ppO2 at which a protein is 50% saturated
P50 Hb is approximately 26 mmHg sometimes referred to as 26 Torr

Question 29

Describe the general trend of the oxygen saturation curve

Answer 29

Hb saturation curve is sigmoidal

Question 30

What happens to tissues with high ppO2? (e.g. alveolar blood)

Answer 30

O2 readily associates with Hb due to positive co-operativity

Question 31

In most tissues, is the ppO2 lower than in alveolar blood?

Answer 31

Yes

Question 32

Why are tissues with high respiratory demand (e.g. skeletal muscle) have a low ppO2?
Approximately 20mmHg

Answer 32

In order to help in terms of rapid dissociation of oxygen from Hb

Question 33

How does positive co-operativity impact Hb?

Answer 33

It improves the efficiency of Hb as an oxygen transporter, allowing rapid delivery of oxygen to tissues

Question 34

What would happen if there was no co-operativity?

Answer 34

An 81-fold increase in ppO2 would be needed to raise oxygen saturation from 10 to 90%

Question 35

What are the range of physiological factors that affects the oxygen binding affinity of Hb?
And hence P50

Answer 35

Temperature
pH
ppCO2
Metabolites e.g. 2,3-BPG, 2,3- DPG