Myoglobin

• Myoglobin is an oxygen-binding protein found in muscle tissue.
• hypoxia caused by 


  deficiency of oxygen at tissues
• the brain is the most sensitive tissue to any deficiency in oxygen
• hypoxia can cause

  • unconsciousness in 15 seconds
  • irreversible brain damage in 2 minutes
  • cell death in 4-5 minutes
• oxygen abundance is measured with partial pressures in

  Torr or mm Hg
• oxygen abundance at sea level is 21% of the air
• atmospheric pressure is ~760 Torr
• in humans myoglobin facilitates the diffusion of oxygen, picking oxygen up at different partial pressures to haemoglobin
• myoglobin structure

  • 75% alpha helical (folded into right hand alpha helices, referred to as A,B...H)
  • 155 amino acids
  • 17 kDa
• interior of the myoglobin molecule consists of non-polar residues except for 2 histidines
• haem group is located in the crevice in the molecule
• to enable oxygen binding to the haem group to be reversible, haem is bound to a protein which acts as the transporter
• haem group gives oxygen-binding capacity on myoglobin and haemoglobin (also gives them colour)
• haem group contains

  • iron atom (Fe2+)
  • protoporphyin IX
• Fe2+ in haem bind to 4 nitrogen atoms in plane, and has 2 other coordination positions on either side of the haem plane (5th and 6th coordination positions)
• 2 histidine residues in helices E and F are

  • distal His (E7)
  • proximal His (F8)
• binding oxygen to (electronic structure) haem causes change in colour
• F8 occupies the 5th coordination position, the iron atom of the haem is directly bonded to it
• iron atom is not directly bonded to E7
• features in myoglobin

  labels

  A) F8, His 93

  B) E7, His 64

  C) F helix

  D) H helix

  E) E helix

  
• E7 (distal histidine) roles

  • reduces affinity of binding carbon monoxide
  • sterically blocks formation of myoglobin associates in which haem-O2-haem sandwiches would form
• CO bind tightly and linearly to myoglobin
• O2 binds more loosely than CO, has a bent structure
• distal His forces bent binding both O2 and CO this

  weakens CO binding
• Le Chatelier's principle 


  if concentration of B is reduced, some of AB mixture will dissociate to release free A and B
• p50 for oxygen binding to myoglobin is 2.75 torr
• Kd and p50 are the same for O2 binding
• myoglobin inside muscle cells facilitates diffusion of oxygen by

  binding oxygen when oxygen concentration is high (at interface with the extracellular fluid)
• myoglobin releases oxygen where oxygen concentration is low (at mitochondria)
• myoglobin facilitates diffusion of oxygen