Haemoglobin and Myoglobin Structure Flashcards
How does myoglobin deliver more O2 than blood?
By storing oxygen in muscles
How much myoglobin do human miscles have?
0.5-0.7 mmol/L myoglobin which is enough for about 7 seconds of intense activity.
The tissue, after it has exhausted its store of myoglobin - where does it depend on for oxygen delivery? (which organ)
The lungs
This is known as muscle globin and has an ancient globin fold that provides a hydrophobic pocket to bind a haem group.
Myoglobin
How many amino acids are there in the primary structure of myoglobin?
150 amino acids
How many secondary structures are there in myoglobin? (include helices and loops)
8 alpha helices (A-H) and connecting loops in between
What is the tertiary structure of myoglobin?
globin fold with hydrophobic pocket (the structure is in the name)
Which amino acid does the haem group in a globin protein bind to?
Histidine F8 (8th amino acid)
What is the quaternary structure of myoglobin?
Monomeric (one polypeptide chain)
This includes four pyrrole rings linked together in a plane. This is a prosthetic group or a cofactor.
Haem/heme
These are structures that bind to proteins or enzymes to enable them to do a certain function. (such as release oxygen)
Cofactors/prosthetic groups
What is the difference between oxyhaemoglobin and deoxyhaemoglobin under spectroscopy?
Oxyhaemoglobin has a bright red colour
Deoxyghaemoglobin has a dull red colour
This is the process by which concentration of dissolved molecules is quantified by wavelength of light and absorbance of light.
Spectroscopy
What gives the haem its characteristic red colour?
Molecular electronic orbitals / Fe2+
The binding of oxygen to the Fe2+ is a what kind of reaction?
Reversible reaction meaning oxygen can bind and unbind from the Fe2+
How is Haem Fe2+ attached to the globin protein? Where does it link?
Histidine F8
This builds on the concept of steric hindrance in that the impossibility of 2 atoms occupying the same space.
Allosteric control
What is an example of allosteric control of oxygen affinity in myoglobin?
Lactate. Lactate reduces myoglobin’s affinity for oxygen but doesn’t bind where it binds
Myoglobin is saturated with ______ at low ____. So it releases this when cellular _____ is very low.
O2, pO2, pO2
The availability of O2 to cellular proteins depends on: (2 things)
pO2 in local environment
binding affinity of O2 to hemoglobin
Hemoglobin in RBCs need to be able to do these: (2 things)
Bind to O2 in the lungs under 100 torr (pO2)
Bind to O2 in the peripheral tissues under 20 torr (pO2)
What did hemoglobin evolved to in terms of binding?
It evolved to binding less tightly on oxygen in comparison to myoglobin because it needs to be able to dump oxygen pretty quickly
This is a tetramer that has four globin proteins associated together non-covalently. It can bond to up to 4 oxygens.
Haemoglobin
This acts as O2 store in the muscle.
Myoglobin
What shape are the crystals (hemoglobic conformations) under aerobic conditions?
Needle shaped
What shape are the crystals (hemoglobic conformations) under anaerobic conditions?
Hexagonal, plate shaped crystals
This type of haemoglobin has a high affinity for oxygen
Oxyhaemoglobin
This type of haemoglobin has a low affinity for oxygen
Deoxyghaemoglobin
This model was proposed in 1965 by Monod, Wyman and Changeux. States that subunits an be in a low activity of high activity conformation. Especially that all subunits must be in the same state.
MWC concerted model
In the MWC concerted model, what does it say about equilibrium?
That binding each substrate shifts equilibrium in favour of R.
These stabilise the T form according to MWC model.
inhibitors
These stabilise the R form according to MWC model.
Acceptors
This model states that one substrate binding induces a T-R conformational change in only one subunit. This conformational change influences the neighbouring subunits and changes their affinity for one substrate; introduces the idea of cooperativity.
KNF sequential model (Koshland, Nemethy, and Filmer)
Where does the oxygen bind to in myoglobin and haemoglobin?
To the haem group
Affinity for oxygen in myoglobin and haemoglobin are altered by _______ binding elsewhere.
molecules (like lactate)
This requires multiple interacting subunits and gives a sigmoidal binding curve.
Cooperativity
This shifts the binding affinity to a physiologically relevant oxygen concentration.
Cooperativity
Approximately how much myoglobin do human muscles have?
0.5-0.7 mmol/L of myoglobin (only enough for about 7 seconds of intense activity)
True or false. The quaternary structure of myoglobin is multimeric and the quaternary structure of haemoglobin is monomeric.
False. Myoglobin is monomeric and haemoglobin is multimeric (tetramer)
How many coordinate bonds does haem have? Where do they bond?
6 coordinate bonds. 4 to nitrogen, 1 to histidine F8 and 1 to O2.
True or false. Haem includes four pyrimidine rings linked together in a plane.
False. Haem includes four pyrrole rings.
This is located on the opposite side of the haem and distorts the binding of gas molecules to the 6th coordination position (of O2) on haem Fe2+.
Histidine E7
What is the purpose of histidine E7?
To reduce the binding affinity of oxygen to myoglobin which will make it easier to release oxygen to the muscle cell.
True or false. Allosteric means without overlapping.
That’s true. In terms of myoglobin, this means having another binding spot for another molecule (like lactate)
What is the partial pressure of oxygen in the lungs and muscle respectively?
100 torr and 20 torr. So the partial pressure of the lungs is higher than that of the muscle.
True or false. Haemoglobin can change shape when dumping oxygens more efficiently in peripheral tissues.
True
True or false. The globin proteins in haemoglobin are associated together with covalent bonds.
False. They are linked to each other with non-covalent bonds.
What’s the difference between the KNF and MWC concerted model?
KNF Sequential Model - states that haemoglobin states change gradually from Tense to Relaxed
> supports positive and negative cooperativity
> support sigmoidal binding curve
MWC Concerted Model - states that haemoglobin states change all at once from Tense to Relaxed. So the state of haemoglobin can only be one or the other.
True or false. Allosteric control is only found in myoglobin.
False. Allosteric control is found in both haemoglobin and myoglobin.
Allosteric control is important for changing the affinity of oxygen via molecules binding elsewhere.
What is the shape of myoglobin and haemoglobin curves? Respectively.
Hyperbolic curve; sigmoidal curve
