Haematology 2 Flashcards
What are globular proteins?
They are spherical, compact proteins (‘spheroproteins’)
Most are water soluble, forming colloids (suspension)
What is the shape, function, solubility (water), AA sequence, stability and examples of globular proteins?
Round/spherical
Functional (catalysts, transport)
Mostly soluble
Irregular
More sensitive to change in heat and pH
Haemoglobin (Hb), insulin, enzymes
What is the shape, function, solubility (water), AA sequence, stability and examples of fibrous proteins?
Long and narrow
Structural (strength, support)
Mostly insoluble
Repetitive
Less sensitive to change in heat and pH
Collagen, keratin, elastin, fibrin
Describe protein structure
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)
What are the functions of proteins?
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)
Tetrameric proteins (4 degrees)
Each with a haem group
How do the subunits interact with each other?
Through hydrogen and ionic bonds (no disulphide bonds)
How is oxygen transported?
In the RBCs by nitrogenous, iron (Fe 2+)- containing pigments- haem groups
What are the three types of Hb in humans?
HbA, HbA2 and HbF
What is HbA?
Major adult Hb
>97%
2 x a-chains
2 x B-chains
What is HbA2?
Minor adult Hb
1-3%
2 x a-chains
2 x sigma-chains
What is HbF?
Fetal Hb
2 x a-chains
2 x y-chains
Features of myoglobin
Related to Hb but only found in muscle tissue (‘myo’)
- Cardiac or skeletal
What type of protein is myoglobin?
Monomeric protein with higher affinity for O2
- 153 AA with a tightly-bound haem group
What is myoglobin used for?
Short-term storage of O2 for muscular contractions
O2 content, capacity & saturation
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
What is oxyhaemoglobin?
Oxyhaemoglobin (O2Hb) is formed by combining 4 x O2 with haem groups.
- Produces blood red colour
- Reversible binding of O2
What is deoxyhaemoglobin?
At low [O2] O2Hb dissociates to deoxyhaemoglobin (HHb) and releases O2
- HHb is a darker deep purple
What does partial pressures mean?
Oxygen and carbon dioxide concentrations are historically expressed as partial pressures
What is partial pressures measured in?
Measured in kPa or mmHg
What does it mean if there is high partial pressure of oxygen?
It is high in alveolar capillaries of the lungs.
Oxygen and Hb combine to form O2Hb
What does it mean if there is low partial pressure of oxygen?
Oxygen dissociates from Hb and diffuses down its concentration gradient into cells via interstitial space
How are the 4 Hb subunits held together?
By 8 strong ionic and many weak hydrogen bonds
What happens when oxygen binding occurs?
It breaks the ionic bonds and forms new hydrogen bonds, relaxing the 4 degree protein structure
What happens when oxygen binding occurs to a haem group in Hb?
It increases oxygen affinities of remaining haem groups
Positive co-operativity
Does myoglobin have positive co-operativity?
Has one globular chain, so there is no positive co-operativity
How many globular chains does haemoglobin have and does it have positive-cooperatively?
4 globular chains and positive co-operativity
Describe the oxygen saturation curve
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
Describe the general trend of the oxygen saturation curve
Hb saturation curve is sigmoidal
What happens to tissues with high ppO2? (e.g. alveolar blood)
O2 readily associates with Hb due to positive co-operativity
In most tissues, is the ppO2 lower than in alveolar blood?
Yes
Why are tissues with high respiratory demand (e.g. skeletal muscle) have a low ppO2?
Approximately 20mmHg
In order to help in terms of rapid dissociation of oxygen from Hb
How does positive co-operativity impact Hb?
It improves the efficiency of Hb as an oxygen transporter, allowing rapid delivery of oxygen to tissues
What would happen if there was no co-operativity?
An 81-fold increase in ppO2 would be needed to raise oxygen saturation from 10 to 90%
What are the range of physiological factors that affects the oxygen binding affinity of Hb?
And hence P50
Temperature
pH
ppCO2
Metabolites e.g. 2,3-BPG, 2,3- DPG
