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• Oxygen saturation curves


  • Different for myoglobin and hemoglobin at different pH's
• Myoglobin oxygen saturation curve

  Hyperbolic, as expected for a monomeric protein
• Hemoglobin oxygen saturation curve

  Sigmoidal, due to oxygenation not being independent
• Oxygen affinity of hemoglobin

  pH dependent
• In the lungs


  Oxygen concentration is high due to oxygenation of hemoglobin and binding of oxygen, release of carbon dioxide
• In muscle tissues


  Oxygen concentration is low and pH is high due to oxygen transfer to muscle and CO2 and H+ binding
• Origin of CO2


  Respiration in muscles resulting in acidic byproducts like lactic acid
• Transport of CO2 in blood plasma

  1. Majority converted to bicarbonate and transported back to lungs

  2. Some transported as carbamate by reaction with amino acid group on hemoglobin
• Histidine residues


  • Normally carry the function of transporting H+ ions due to their basic characteristics, His 146 (beta) and His 122 (alpha) involved in this process
• Hemoglobin structure


  Compact, containing globin chains that interact through salt bridges, in a tense state
• Cooperativity in oxygen binding to hemoglobin

  1. Addition of first oxygen is difficult, Fe(II) goes from high spin to low spin, causing iron to shrink and move with proximal histidine chain

  2. Globin chain moves in same direction

  3. Hemoglobin relaxes when salt bridges break and structure opens up, allowing easy binding of 2nd, 3rd and 4th oxygen
• Myoglobin


  Not an allosteric protein
• Hemoglobin


  An allosteric protein, where interactions at one site affect remote sites
• Oxygen binding at one site of hemoglobin


  Allows other oxygen molecules to bind at other sites
• H+ and CO2 binding to hemoglobin

  Promotes formation of salt linkages, putting hemoglobin in a tense state which squeezes out oxygen
• This is physiologically important as it enhances oxygen release in metabolically active tissues where oxygen is required
• Oxygen binding to hemoglobin in alveolar capillaries

  Leads to breakage of salt linkages, releasing CO2 and H+
• Bohr effect


  Oxygen binding to hemoglobin is inversely related to concentration of CO2 and H+
• Haldane effect


  At lower oxygen saturation levels, carbon dioxide will effectively bind to hemoglobin
• Haldane effect impacts


  Unloading of O2 and unloading of CO2
• Venous blood


  Has increased carrying capacity of CO2 due to unloading of O2 in peripheral capillaries
• In lung capillaries


  Hemoglobin oxygenation enhances unloading of CO2 from hemoglobin, facilitating pulmonary excretion of CO2
• In the lungs


  1. Oxygen binding to hemoglobin leads to relaxed state, breaking salt linkages, allowing more oxygen to bind

  2. This changes pKa, releasing H+ ions from histidine residues

  3. Released H+ ions react with HCO3 to produce CO2 which is exhaled

  4. Oxygen binding destabilizes carbamate groups on globin chains, leading to release of more CO2
• Adaptive allosteric interactions


  BPG has a binding site on hemoglobin, stabilizing the tense state and reducing oxygen affinity
• This slight reduction in oxygen saturation allows hemoglobin to release oxygen more efficiently to tissues
• Carbon monoxide


  Colorless, odorless gas produced by incomplete combustion, 25 times greater affinity to myoglobin compared to oxygen
• Affinity of carbon monoxide to hemoglobin

  25,000 times greater than oxygen if there is no hydrogen bonding and the Fe-C≋O is linear