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7.3.2: Oxygen Transport by the Proteins Myoglobin and Hemoglobin

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    360925
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    Oxygen Transport 

    Many microorganisms and most animals obtain energy by respiration, the oxidation of organic or inorganic molecules by O2. At 25°C, however, the concentration of dissolved oxygen in water in contact with air is only about 0.25 mM. Because of their high surface area-to-volume ratio, aerobic microorganisms can obtain enough oxygen for respiration by passive diffusion of O2 through the cell membrane. As the size of an organism increases, however, its volume increases much more rapidly than its surface area, and the need for oxygen depends on its volume. Consequently, as a multicellular organism grows larger, its need for O2 rapidly outstrips the supply available through diffusion. Unless a transport system is available to provide an adequate supply of oxygen for the interior cells, organisms that contain more than a few cells cannot exist. In addition, O2 is such a powerful oxidant that the oxidation reactions used to obtain metabolic energy must be carefully controlled to avoid releasing so much heat that the water in the cell boils. Consequently, in higher-level organisms, the respiratory apparatus is located in internal compartments called mitochondria, which are the power plants of a cell. Oxygen must therefore be transported not only to a cell but also to the proper compartment within a cell.

    Myoglobin and Hemoglobin 

    Myoglobin is a relatively small protein that contains 150 amino acids. The functional unit of myoglobin is an iron–porphyrin complex that is embedded in the protein (Figure 4.2.1). In myoglobin, the heme iron is five-coordinate, with only a single histidine imidazole ligand from the protein (called the proximal histidine because it is near the iron) in addition to the four nitrogen atoms of the porphyrin. A second histidine imidazole (the distal histidine because it is more distant from the iron) is located on the other side of the heme group, too far from the iron to be bonded to it. Consequently, the iron atom has a vacant coordination site, which is where O2 binds.

    2fd893096fd390a15e2e1c9058145cf9.jpg
    Figure \(\PageIndex{1}\). The Structure of Deoxymyoglobin, Showing the Heme Group. The iron in deoxymyoglobin is five-coordinate, with one histidine imidazole ligand from the protein. Oxygen binds at the vacant site on iron.

    In the ferrous form (deoxymyoglobin), the iron is five-coordinate and high spin. Because high-spin Fe2+ is too large to fit into the “hole” in the center of the porphyrin, it is about 60 pm above the plane of the porphyrin. When O2 binds to deoxymyoglobin to form oxymyoglobin, the iron is converted from five-coordinate (high spin) to six-coordinate (low spin; Figure 4.2.2). Because low-spin Fe2+ and Fe3+ are smaller than high-spin Fe2+, the iron atom moves into the plane of the porphyrin ring to form an octahedral complex. The O2 pressure at which half of the molecules in a solution of myoglobin are bound to O2 (P1/2) is about 1 mm Hg (1.3 × 10−3 atm).

    cb5cc187d5f3c957e984d6c0d6feb91b.jpg
    Figure \(\PageIndex{2}\).  Oxygen Binding to Myoglobin and Hemoglobin. (a) The Fe2+ ion in deoxymyoglobin is high spin, which makes it too large to fit into the “hole” in the center of the porphyrin. (b) When O2 binds to deoxymyoglobin, the iron is converted to low-spin Fe3+, which is smaller, allowing the iron to move into the plane of the four nitrogen atoms of the porphyrin to form an octahedral complex.

    Hemoglobin consists of two subunits of 141 amino acids and two subunits of 146 amino acids, both similar to myoglobin; it is called a tetramer because of its four subunits. Because hemoglobin has very different O2-binding properties, however, it is not simply a “super myoglobin” that can carry four O2 molecules simultaneously (one per heme group). The shape of the O2-binding curve of myoglobin can be described mathematically by the following equilibrium:

    \[M b O_{2} \rightleftharpoons M b+O_{2}\]

    \[K_{d i s s}=\frac{[M b]\left[O_{2}\right]}{\left[M b O_{2}\right]}\]

    The O2-binding curve of hemoglobin is S shaped (Figure 4.2.3). As shown in the curves, at low oxygen pressures, the affinity of deoxyhemoglobin for O2 is substantially lower than that of myoglobin, whereas at high O2 pressures the two proteins have comparable O2 affinities. The physiological consequences of unusual S-shaped O2-binding curve of hemoglobin are enormous. In the lungs, where O2 pressure is highest, the high oxygen affinity of deoxyhemoglobin allows it to be completely loaded with O2, giving four O2 molecules per hemoglobin. In the tissues, however, where the oxygen pressure is much lower, the decreased oxygen affinity of hemoglobin allows it to release O2, resulting in a net transfer of oxygen to myoglobin.

    4c03b82629075afcfa08072e1981afdb.jpg
    Figure 4.2.3: The O2-Binding Curves of Myoglobin and Hemoglobin. Plots of Y (fractional saturation) vs L (pO2) are hyperbolic for Mb, but sigmoidal for Hb, suggesting cooperative binding of oxygen to Hb (binding of the first oxygen facilitates binding of second, etc).

    The S-shaped O2-binding curve of hemoglobin is due to a phenomenon called cooperativity, in which the affinity of one heme for O2 depends on whether the other hemes are already bound to O2. Cooperativity in hemoglobin requires an interaction between the four heme groups in the hemoglobin tetramer, even though they are more than 3000 pm apart, and depends on the change in structure of the heme group that occurs with oxygen binding. The structures of deoxyhemoglobin and oxyhemoglobin are slightly different, and as a result, deoxyhemoglobin has a much lower O2 affinity than myoglobin, whereas the O2 affinity of oxyhemoglobin is essentially identical to that of oxymyoglobin. Binding of the first two Omolecules to deoxyhemoglobin causes the overall structure of the protein to change to that of oxyhemoglobin; consequently, the last two heme groups have a much higher affinity for Othan the first two.

    The affinity of Hb, but not of Mb, for dioxygen depends on pH. This is called the Bohr effect, after the father of Neils Bohr, who discovered it.

    clipboard_e6f9fe5f4de40d739f7f3f4ef47fa44d3.png
    Figure 4.2.4: The Bohr Effect

    Decreasing pH shifts the oxygen binding curves to the right (to decreased oxygen affinity). Increased [H+] will cause protonation of basic side chains. In the pH range for the Bohr effect, the mostly likely side chain to get protonated is His (pKa around 6), which then becomes charged. The mostly likely candidate for protonation is His 146 (on the β chain - CH3) which can then form a salt bridge with Asp 94 of the β(FG1) chain. This salt bridge stabilizes the positive charge on the His and raises its pKa compared to the oxyHb state. Carbon dioxide binds covalently to the N-terminus to form a negatively charge carbamate which forms a salt bridge with Arg 141 on the alpha chain. BPG, a strongly negatively charged ligand, binds in a pocket lined with Lys 82, His 2, and His 143 (all on the beta chain). It fits into a cavity present between the β subunits of the Hb tetramer in the T state. Notice all these allosteric effectors lead to the formation of more salt bridges which stabilize the T or deoxy state. The central cavity where BPG binds between the β subunits become much smaller on oxygen binding and the shift to the oxy or R state. Hence BPG is extruded from the cavity.

    The binding of H+ and CO2 helps shift the equilibrium to deoxyHb which faciliates dumping of oxygen to the tissue. It is in respiring tissues that CO2 and H+ levels are high. CO2 is produced from the oxidation of glucose through glycolysis and the Krebs cycle. In addition, high levels of CO2 increase H+ levels through the following equilibrium:

    \[\mathrm{H}_{2} \mathrm{O}+\mathrm{CO}_{2} \rightleftharpoons \mathrm{H}_{2} \mathrm{CO}_{3} \rightleftharpoons \mathrm{H}^{+}+\mathrm{HCO}_{3}^{-}\]

    In addition, H+ increases due to production of weak acids such as pyruvic acid in glycolysis .

    Hb, by binding CO2 and H+, in addition to O2, serves an additional function: it removes excess CO2 and H+ from the tissues where they build up. When deoxyHb with bound H+ and CO2 reaches the lungs, they leave as O2 builds and deoxyHb is converted to oxyHb.


    7.3.2: Oxygen Transport by the Proteins Myoglobin and Hemoglobin is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.