Heamoglobin Flashcards
What type of metabolism does haemoglobin play a role in?
Aerobic respiration - involved primarily in transfer of Oxygen.
What determines the binding of oxygen to Haemoglobin?
The haem groups. it’s not part of the polypeptide chain however, it’s tightly bound to the protein.
Describe the structure of Haemoglobin.
Haemoglobin is a quartenary structure with 4 polypeptide chains. It can bind 4 oxygens. These subunits are held together by non-covalent interactions.
What non covalent interactions are involved in Haemoglobin?
1- VDW interactions.
2- Electrostatic forces.
3- Hydrogen bonds.
What is the function of Haemoglobin?
1- To transport Oxygen to tissues.
2-To transport coz and protons away from tissues.
Discuss the schematics of oxygen binding site.
The site at which oxygen binds in both Hb and myoglobin is the haem which is found in the hydrophobic pocket of the protein. At the center of this is an iron atom held in place by 4 nitrogens.
What holds the haem groups in the correct position within the hb chain?
The proximal histidine (f8) directly bonds to the iron in the haem and pulls it out of the frame. To prevent complete dislocation of the iron, and oxygen molecule binds also to the iron and pulls it back to the plane. This oxygen molecule is also bonded to the distal histidine (E7) which also contributes to the position of the haem.
What is myoglobin?
Oxygen reservoir within the heart and skeletal muscles cells.
Consists of 8 helices- A to H.
Non helical region= A to B and B to C.
Which of the 2 has a higher affinity for oxygen: myoglobin or haemoglobin?
Myoglobin- it doesn’t have a quaternary structure (monomer) therefore binding oxygen more tightly that hb. This difference in binding energy results in a hyperbolic shape in the oxygen dissociation curve.
What are the variant forms of hb and how are they expressed?
HbA- adult
HbA2- minor adult form
HbF-foetal form
Hb Gower1- embryonic
Hb Gower2- embryonic
Hb Portland- embryonic
What is sickle haemoglobin?
Arises from the single substitution of the amino acid glutamate to valine in hb. This causes hb molecules to distort and form a sickle shape.
What are the effects of sickle cell anaemia?
1- Distorted shape leads to stacking of HbS into long fibres at low oxygen concentrations.
2- RBC looses its flexibility and affinity for oxygen drops.
3- Results in blockage of capillaries which can result in anoxia in tissues (leads to cell death).
4- Typically results in infection, dehydration, cold and hypoxia.
Describe the clinical consequences of sickle cell anaemia.
1-Bone pain resulting from blockages.
2-Chronic anaemia- destruction of erythrocytes.
3-Cerebrovascular accidents.
4-Organ damage (kidneys, heart and lungs).
5-Acute crisis- very painful.
What are the methods of diagnosing sickle cell anaemia and what are probable treatments?
Diagnosing: protein or genetic analysis.
Treatment:
1- most symptom management (hydration and analgesics).
2- Aggressive abx.
3- Blood transfusion (grey area as it can lead to iron overload).
4- Hydroxyurea.
Discuss hydroxyurea as treatment option for sickle cell anaemia.
Anti cancer drug primarily. Changes gene expression to increase levels of foetal hb which is not normally expressed in adults. Foetal hb has a higher affinity for oxygen and it’s levels are ^ by approx 40%.