O2 Transport and Storage

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O2 Transport and Storage
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O2 is essential for animals
Low O2 solubility in aqueous solution (0.2 ml in
100 ml plasma) ? need some ways to carry O2
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Respiratory metal-containing proteins

• ? Hemoglobin (Hb) Fe
• vertebrates (blood cells), echinoderms,
  annelids,
• molluscs, insect larvae
• ? Chlorocurorin Fe (similar to myoglobin)
• annelids
• ? Hemerythrin (Hr) Fe
• marine invertebrates, annelids
• ? Hemocyanin (Hc) Cu
• molluscs and arthropods

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Dioxygen Carriers
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Hemoglobin, an historical protein
? First protein to be crystallized in 1849 ?
First protein to have its mass accurately
measured. ? First protein to be studied by
ultracentrifugation. ? First protein to
associated with a physiological condition. ?
First protein to show that a point mutation can
cause problems. ? First proteins to have X-ray
structures determined
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Hemoglobin (Hb)
Hemoglobin is an ?2?2 heterodimer
? and ? chains identical 3-D structure ( gt45
sequence homology )
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Myoglobin (Mb)
Myoglobin is a monomer
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Hb ? and ? chains and Mb Sequences
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Mb and Hb share the same fold
but Hb is oligomeric and Mb monomeric
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Hemoglobine function
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Hemoglobin vs. Myoglobin
Hb is designed for fixing O2 in lungs and
releasing it in tissues ? O2 carrier Mb is
designed for keeping it in tissues ? O2 storage
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How does Hb work?
Hb O2 ? HbO2 O2 ? Hb(O2)2 O2 ? Hb(O2)3
O2 ? Hb(O2)4
The sigmoidal shape (Hb) vs. hyperbolic (Mb) for
O2 binding ? the binding of O2 at one site
increases the affinity for O2 at the other sites
in the same Hb molecule
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The Hill plotlog?/(1-?) vs. logO2
Hb nO2 ? Hb(O2)n
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The Hill number nH

• The slope n is equal to the number of the binding
  sites (i.e. 4 for Hb).
• In reality, it is never n, and is called nH, the
  Hill coefficient

nH reflects the degree of cooperativity between
the binding sites. For Hb, nH 2.8-3.0
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Cooperativity allosteric effect
Binding 1 O2 loosens conformation of Hb
subunits and favor the binding of the 3 other O2
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Cooperativity allosteric effect
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Important rearrangementin the quaternary
structure
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Important rearrangementin the quaternary
structure
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2,3-Bisphosphoglycerate (2,3-BPG)stabilizes the
T-form
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Hemoglobin, active site
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Nature of Fe-O2 bonding in Hb/Mb and models
Deoxy-forms are paramagnetic ? Fe(II) d6 high
spin (S 2)
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Fe(III) d5 low spin O2- ligand
C. A. Reed and S. K. Cheung Proc. Natl. Acad.
Sci. USA 1977, 74, 1780
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Oxy-Hb is a Fe(III)O2-
Raman ?OO 1105 cm-1
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Structural modifications du to O2-binding
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Movement of Fe into heme plane
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Structural modifications du to O2-binding
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Structural modifications du to O2 binding (end).
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Rearrangement changes the H-bonds
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Important rearrangementin quaternary structure
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Hemerythrin (Hr)
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deoxy-Hr active site
?-oxo or ?-hydroxo
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oxy-Hr active site
superoxo or peroxo
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Hemerythrin
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Hemocyanine (Hc)
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Coordination modes for O2 to a binuclear Cu center
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oxy-Hc structure
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O2 carriers 3 different strategies