Oxygen tra

• Metanoun organisms


  Organisms that evolved 0.5 x 10^9 years ago and became dependent on an oxygen (O2)-based recovery of energy from chemical bonds
• Vertebrates


  • Aerobic organisms with a closed circulatory system and a mechanism for extraction of O2 from air (or water) and release of carbon dioxide (CO2) in waste products
• Inspired O2


  Leads to an efficient utilisation of metabolic fuels, such as glucose and fatty acids
• Expired CO2


  A major product of cellular metabolism
• Utilization of O2 as a metabolic substrate

  Accompanied by the generation of free radical species that are capable of damaging virtually all biological macromolecules
• Organisms protect themselves from radical damage

  • By sequestering O2, limiting their production and scavenging these
• Heme proteins


  Participate in these protective mechanisms
• Major heme proteins in mammals

  • Myoglobin (Mb)
  • Hemoglobin (Hb)
• Myoglobin (Mb)


  Found predominantly in skeletal and striated muscle and serves to store O2 in the cytoplasm and deliver it on demand to the mitochondria
• Hemoglobin (Hb)


  Restricted to erythrocytes where it facilitates the transport of O2 and CO2 between the lungs and peripheral tissues
• The introduction of O2 into the Earth's anaerobic biosphere occurred ~2.5 x 10^9 years ago and led to its current level in air of 21%
• Partial pressure of a gas


  A specific contribution of each component in a mixture of gases, directly proportional to its concentration (Dalton's Law)
• For atmospheric O2 at a barometric pressure (sea level) of 760 mmHg or torr (101.3 kPascal or kPa = 1 atmosphere absolute or ATA), the partial pressure of oxygen, pO2, is 150-160 mmHg
• The amount of O2 in solution is directly proportional to its partial pressure
• In arterial blood (37°C, pH 7.4) the pO2 is ~100 mmHg, which produces a concentration of dissolved O2 of 0.13 mmol/L
• The level of dissolved O2 is inadequate to support efficient aerobic metabolism
• Hemoglobin (Hb)


  A tetrameric protein with four O2-binding sites (heme groups)
• In arterial blood with a Hb concentration of 150 g/L (2.3 mmol/L) and O2 saturation of 97.4%, the contribution of protein-bound O2 is about 8.7 mmol/L
• This concentration of protein-bound O2 represents a dramatic 67-fold increase over physically dissolved O2
• The total oxygen-carrying capacity of arterial blood, in dissolved and protein-bound forms, is ~8.8 mmol/L, almost 200 ml of dissolved oxygen per liter of blood
• Globins


  • An ancient family of soluble metalloproteins whose structure and functions have been characterized in microorganisms, plants, invertebrates, and vertebrates
  • Present day globins, with their spectacular diversity of function, most likely evolved from a single ancestral globin
• The extent of amino acid identity among invertebrate and vertebrate globins varies widely and can often appear random
• Globins


  • Two features are noteworthy: the invariant residues PheCD1 and HisF8 and characteristic patterns of hydrophobic residues in helical segments
• Human myoglobin (Mb)


  A single globin polypeptide (153 amino acid residues, 17,053 Da)
• Human hemoglobin (Hb)


  A tetrameric assembly of two α-globin polypeptides (141 residues, 15,868 Da) and two β-globin polypeptides (146 residues, 15,126 Da)
• A single heme prosthetic group is noncovalently associated with each globin apoprotein
• Mammalian globins


  • The secondary structure is dominated by a high proportion of α-helices, with over 75% of the amino acids associated with eight helical segments
  • These α-helices are organized into a tightly packed, nearly spherical, tertiary structure, designated the globin fold
• The conventional nomenclature for globin residues follows that defined initially for sperm whale Mb, with residues numbered within each helix and corner
• Polar amino acids


  Located almost exclusively on the exterior surface of globin polypeptides and contribute to the remarkably high solubility of these proteins
• Hydrophobic residues


  Buried within the interior, where they stabilize the folding of the polypeptide and form a pocket that accommodates the heme prosthetic group
• Histidines


  • Play indispensable roles deep within the heme pocket
  • The side chain of the proximal histidine (HisF8) is close enough to bond directly to the pentacoordinate Fe atom
  • The distal histidine (HisE7) functions critically to stabilize bound O2 by hydrogen bonding
• Heme prosthetic group


  A porphyrin molecule to which an iron atom (Fe) is coordinated<|>The Fe-porphyrin prosthetic group is planar and hydrophobic, with the two propionate groups exposed to solvent<|>Heme becomes an integral component of the globin holoprotein during polypeptide synthesis, giving globins their characteristic purple-red color
• Myoglobin (Mb)


  Located in the cytosol of skeletal, cardiac and some smooth muscle cells, Mb holds O2 that has been released by Hb in the tissue capillaries and subsequently diffused into this compartment<|>This stored O2 is readily available to organelles, particularly the mitochondrion, that carry out oxidative metabolism
• Reversible reaction of Mb with O2

  Mb + O2 ⇌ MbO2
• Equilibrium constant (K')


  Affinity or equilibrium constant for the reversible binding of O2 to Mb
• Fractional O2 saturation (Y)

  The fraction of Mb binding sites occupied by O2
• The equation for the O2 saturation curve of Mb describes a hyperbola with a P50 (the value of pO2 at which Y=0.5) of 4 mmHg
• The low value of P50 reflects a high affinity for O2
• In the capillary beds of muscle tissues, pO2 values are in the range of 20-40 mmHg
• Working muscles exhibit lower pO2 values than muscles at rest