Proteins in Action 1 Flashcards
What is the problem of oxygen availability in animals?
Highly active tissue e.g. exercising muscle or brain, is limited by the availability of oxygen. There is strong evolutionary pressure for efficient oxygen transport and delivery
What is myoglobins function?
It challenges the oxygen in muscles against bursts of high requirements. Resides in muscles and stores oxygen, present in a modest concentration. Human muscles have 0.5-0.7mmol/L (enough for 7sec of intense activity)
What is myoglobin?
Protein primary structure: ~150 amino acids
Secondary: 8 a-helix A-H and connecting loops
Tertiary: globin fold with hydrophobic pocket (helps protein bind to haem group)
Quaternary: monomeric (single polypeptide chain)
What is haem group?
Haem includes four pyrrole rings linked in a plane. Iron has six coordinate bonds - four to nitrogen atoms of haem, one to N of histidine F8 the globin and one to oxygen, molecule orbitals give it its red colour, binding of oxygen to iron is reversible
Which interactions break and reform during myoglobins function?
His E7 interacting with oxygen and oxygens interaction with iron
How is spectroscopy related to oxygen binding in globins?
Shape of spectrum differs with colour and chemical nature of solute
Protein is colourless. Haem is bright red if oxygenated blood and dull red if deoxygenated
What is myoglobins haem interaction with oxygen?
Haem Fe2+ is attached to globin protein by co-ordinate linkage to His F8. His 7 is located on opposite side of haem and distorts binding of gas molecules reducing binding affinity of oxygen making it easier for oxygen to be released to muscle cell
How do myoglobin and haemoglobin show allosteric control?
Allosteric means without overlapping, controlled differently
Lactate decreases myoglobins affinity for oxygen but does not bind where oxygen binds, lactate build up promotes oxygen release increase availability for respiration
How do myoglobin and haemoglobin differ in O2 binding?
Myoglobin saturated with O2 at low partial pressure of O2 (pO2) only release O2 to muscle cells when cellular pO2 is very low
Partial pressure of oxygen in lungs is ~ 100 Torr, muscle ~ 20 Torr
Haemoglobin functions as an O2 transporter hence has a much weaker binding affinty for oxygen, sigmoidal curve
Two facts affecting oxygen binding to myoglobin and haemoglobin?
pO2 in local environment and binding affinity of O2 to haemoglobin
Haemoglobin oxygen binding and release process:
Haemoglobin in red blood cells needs to be able to bind O2 in the vicinity of the lungs were pO2 is ~100Torr and release O2 in the vicinity of peripheral tissue where pO2 is ~20Torr
Evolved to bind O2 less tightly than myoglobin, evolved to be a Tetramer (four globin proteins associated non-covalently) and can change shape
What is the MWC concentrated model?
Subunits can be in low-activity, tense (T) or high activity, relaxed (R)
All subjects must be in same state. Binding each successive substrate (S) shifts equilibrium in favour of R. Inhibitors stabilise T form, activators stabilise R form
What is the KNF model?
One substrate binding induces T->R conformational change in only one subunit, influences neighbouring subunits to change their affinity, explains positive and negative cooperation
Both haemoglobin and myoglobin:
Oxygen binds to iron of haem, shift from dull to bright red allows monitoring O2 binding, affinity for oxygen altered by molecules binding elsewhere (allosteric control)
Myoglobin versus haemoglobin:
Monomer vs. tertamer
Tighter, hyperbolic vs. weaker, sigmoidal binding curve
Store in tissue vs. transport molecule
