Myoglobin

1
Myoglobin Hemoglobin

• BG320
• Structure Function of Biomolecules

2
Oxygen Transport Proteins

• Myoglobin
• Exhibits Michaelis-Menten properties
• Hemoglobin
• Exhibits allosteric properties

3
Myoglobin

• Single polypeptide
• 16,700 daltons
• 8 a helices (A-H)
• Located in skeletal cardiac muscle
• high in diving mammals like whale seals

Heme prosthetic group
http//www.agen.ufl.edu/chyn/age2062/lect/lect_02
/3_27.gif
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Heme Prosthetic Group

• Heme (Fe2) has affinity for O2.
• Hematin (Fe3) cannot bind O2.
• Located in crevice where it is protected from
  oxidation.

5
Oxygen Binding to Myoglobin
distal histidine

• O2 binds to only available coordination site on
  iron atom.
• His 93 (proximal his) binds directly to iron.
• His 64 (distal his) stabilizes the O2 binding
  site.

proximal histidine
http//cwx.prenhall.com/horton/medialib/media_port
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O2 Binding Curve

• Myoglobin has high affinity for O2.
• P50 2.8 Torr
• Allows myoglobin to act as O2 storage reserve.
• Releases O2 when pO2 becomes low indicating O2
  deprivation.

7
Hemoglobin

• Heterotetramer
• HbA (most common)
• a2b2
• 2 dimers
• a1b1 and a2b2

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Hemoglobin Structure

• Each polypeptide chain resembles myoglobin
  tertiary structure but 1 sequence varies.
• Invariant residues indicate importance of those
  residues in function.

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Oxygen Binding
(R state)
(T state)
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O2 Binding to Hemoglobin

• Hb exhibits cooperativity.

http//cwx.prenhall.com/horton/medialib/media_port
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Hb Variants

• HbA2
• a2d2
• Present in 2 of adults
• Embryonic Hb
• a2e2
• Has ? affinity for O2
• Fetal Hb
• a2g2
• Has ? affinity for O2

http//oregonstate.edu/instruction/bb450/stryer/ch
10/Slide27.jpg
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Bohr Effect

• ?CO2 ?pH
• Some side groups remain protonated at lower pH.
• Stabilizes T state and promotes unloading of O2
  to active tissues.
• Binding of CO2 also stabilizes T state.
• CO2 binds to a amino groups.

http//cwx.prenhall.com/horton/medialib/media_port
folio/text_images/FG04_50.JPG
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2, 3-Bisphosphoglycerate

• Stabilizes deoxyHb (T state)
• Facilitates unloading of O2 in tissue.

100
- BPG
saturation with O2
50
BPG
20
100
pO2 (partial pressure of O2) (Torr)
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2,3-BPG Binding to Hb
http//oregonstate.edu/instruction/bb450/stryer/ch
10/Slide26.jpg
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High Altitude and BPG

• At higher altitudes, the BPG increases allowing
  Hb to unload O2 more easily.

http//www.bio.davidson.edu/Courses/anphys/1999/Yu
si/dpgoxyhbgraph.jpg
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Stored Blood BPG

• 2,3-BPG becomes depleted in stored blood, so R
  state of Hb is stabilized.
• If BPG depleted blood is used for a transfusion,
  the R state Hb doesnt release O2.
• Add inosine to stored blood to maintain BPG
  levels.

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CO Poisoining

• CO is competitive inhibitor of O2.
• Affinity is 200X greater than that of O2.
• CO also inhibits unloading O2 of in tissues.