Session 2 Flashcards
How is the Fe atom bound to haemoglobin or myoglobin?
Via the proximal histidine residue on the other side of the haem group to the oxygen binding site.
What happens to deoxymyoglobin when oxygen binds to it?
The Fe is pulled slightly into the plane of the ring structure, causes a small change in overall protein conformation.
What relationship does oxygen show when binding to myoglobin?
A hyperbolic relationship, very low partial pressures of oxygen give 50% saturation in myoglobin.
What relationship does oxygen binding to haemoglobin show and why?
Sigmoidal relationship, oxygen binding promotes the R state of Hb so as more oxygen binds, more oxygen is likely to bind so a Sigmoidal relationship is shown.
What is the low oxygen affinity state of Hb called?
Tensile (T) state.
What is the high affinity state of Hb called?
Relaxed (R) state.
How is oxygen binding to Hb regulated?
Using 2,3-BPG, it acts as an inhibitor by reducing the affinity of O2 to Hb (promotes the T state), only 1 BPG molecule can bind per Hb tetramer
When does [2,3-BPG] increase and why?
Increases at high altitudes.
Promotes oxygen release in the tissues at high altitudes because [oxygen] is lower.
What is the Bohr effect?
Haemoglobin’s oxygen binding affinity is inversely related to both acidity and concentration of carbon dioxide.
How does carbon monoxide affect haemoglobin?
It combines with ferromyoglobin and ferrohaemoglobin to block oxygen transport, binds 250x more strongly than oxygen and also increases the affinity of other unaffected subunits to oxygen.
At what concentration does carbon monoxide become fatal?
50%
How are the glob in chains in adult, foetal and adult2 haemoglobin arranged?
HbA: 2 alpha and 2 beta chains
HbF: 2 alpha and 2 gamma chains
HbA2: 2 alpha and 2 delta chains
Why is HbF useful?
Has a higher binding affinity for oxygen than HbA (dissociation curve moves to the left) so oxygen can be transferred from the mothers blood supply to the foetus.
What mutation causes sickle cell anaemia?
A to T; Glutamine to Valine in the beta glob in chains.
What causes cell sickling in sickle cell anaemia?
Mutation to Valine causes a hydrophobic pocket to form, allows deoxygenated HbS to polymerise and become sickle shaped.
What properties do sickle cells have?
More prone to lyse
More rigid
What are beta-thalassaemias and when do symptoms appear?
Decreased or absent production of beta-glob in chains so alpha-chains can’t form stable tetramers.
Symptoms appear after birth as beta-chains aren’t present in HbF.
What are alpha-thalassaemias and when do symptoms appear?
Decreased or absent alpha-globin production, there are several different severities due to multiple copies of alpha-chains present. Beta-chains can form stable tetramers with increased oxygen affinity.
Symptoms appear before birth because alpha chains are present in HbF
What is the transition state of a chemical reaction?
The high energy intermediate that lies between the substrate and product states.
What is the activation energy of a reaction?
The minimum energy substrates must have to allow the reaction to progress.
How can the rate of a reaction be increased?
Increase temperature: more molecules have activation energy.
Increase substrate conc: increases chances of molecular collisions.
Enzymes: lowers activation energy to facilitate formation of the transition state.
What properties do enzymes possess?
Highly specific Unchanged after a reaction Don't affect reaction equilibrium Increase rate of reaction Most are proteins and may require cofactors
What is the active site of an enzyme?
The site where substrates bind and the chemical reaction occurs (usually a cleft or crevice).
What forms the active site of an enzyme?
Amino acids from different parts of the primary sequence.
