Myoglobin

• what is hypoxia?

  Insufficient oxygen supply to tissues.
• what can hypoxia lead to?

  Unconsciousness (15 sec)

  irreversible brain damage (2 min)

  cell death (4-5min)
• do humans have an oxygen store?

  no
• what happens to oxygen conc?

  when moves from air to intracellular environment amount and conc gets lower
• can humans rely on diffusion?

  No, too large and require a transport system
• what must myoglobin have?

  bind reversible
• what do we measure?

  Abundance of oxygen at particular location, measured in partial pressure
• what is partial pressure measured in?

  Torr, mm of Hg
• what is the partial pressure of oxygen?

  155.5 torr
• what happens to the partial pressure of oxygen from environment to mitochondria?

  falls
• what faciliates diffuses oxygen?

  myoglobin
• where does myoglobin act?

  intracellular
• where was myogloin first purified from?

  whale blood - Max Perutz in 1958
• how many amino acids are in myoglobin?

  155 amino acids
• what is the major structure of myoglobin?

  75% alpha helices
• what are helical segments terminated by?

  proline residues
• why does proline terminate helices?

  cyclic aa with a locked conformational angle
• what is the solubility of oxygen in water?

  1 x10^-4
• why can't heme be used by itself?

  it binds to oxygen irreversibly
• why does haemoglobin allow heme to reversibly bind?

  as it lowers affinity, so acts a transporter
• what gives myoglobin and haemoglobin its colour?

  non-polypeptide haem
• what is the 3d structure of haem?

  flat
• how many atoms can iron bind to?

  6
• what is the iron atom bound to?

  protoporphyin IX
• what happens to colour when oxygen binds to heme?

  changes colour, bright scarlet colour of oxygenated blood,

  dark purple colour od deoxygenated
• what are the two histidine residues in helices in E and F?

  Distal His (E7)

  Proximal His (F8)
• the iron atom directly bonds to what?

  F8 of proximal and occupies 5th coordination position
• where does the oxygen sit in myoglobin/haemoglobin?

  between iron group of his and E7 his
• what is the function of histidine E7?

  reduces affinity of binding carbon monoxide

  sterically blocks the formation of haem-O2-haem sandwich
• what does le chaterlier tells us what occurs if oxygen is low?

  oxygen dissociation from myoglobin
• what is the partial pressure at 50% saturation?

  2.75 torr
• dissociation constant for myoglobin is the same as?

  p50
• why does carbon monoxide stop oxygen bind?

  CO binds tightly with a linear structure
• why does the distal his weaken CO binding?

  As it forces bent binding of both
• which position does distal histidine take?

  6th coordination position
• What is the interior of myoglobin like?

  consist almost entirely of non-polar residues
• where is the haem group located on myoglobin?

  in the crevice

  Surrounded by non-polar residues except for two histidines