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OBJECTIVES
After studying this chapter, you should be able to:
Describe the most important structural similarities and differences between myoglobin and hemoglobin.
Sketch binding curves for the oxygenation of myoglobin and hemoglobin.
Identify the covalent linkages and other close associations between heme and globin in oxymyoglobin and oxyhemoglobin.
Explain why the physiologic function of hemoglobin requires a sigmoidal rather than hyperbolic O2-binding curve.
Explain the role of the distal histidine on the ability of hemoglobin to bind carbon monoxide (CO).
Define P50 and indicate its significance in oxygen transport and delivery.
Describe the structural and conformational changes in hemoglobin that accompany its oxygenation and subsequent deoxygenation.
Explain the role of 2,3-bisphosphoglycerate (BPG) in oxygen binding and delivery.
Explain how the Bohr effect enhances the ability of red blood cells to transport CO2 and deliver it to the lungs.
Describe the structural consequences to hemoglobin S (HbS) of lowering Po2.
Identify the metabolic defect that occurs as a consequence of α and β thalassemias.
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BIOMEDICAL IMPORTANCE
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The efficient delivery of oxygen from the lungs to the peripheral tissues and the maintenance of tissue reserves to protect against anoxic episodes are essential to health. In mammals, these functions are performed by the homologous heme proteins hemoglobin and myoglobin, respectively. Myoglobin, a monomeric protein of red muscle, binds oxygen tightly as a reserve against oxygen deprivation. The multiple subunits of hemoglobin, a tetrameric protein of erythrocytes, interact in a cooperative fashion that enables this transporter to offload a high proportion of bound O2 in peripheral tissues while simultaneously retaining the capacity to bind it efficiently in the lungs. In addition to delivering O2, proton binding to hemoglobin aids in the transport of CO2, a major product of respiration, to the lungs for disposal. Oxygen delivery is enhanced by the binding of 2,3-bisphosphoglycerate (BPG), which stabilizes the quaternary structure of deoxyhemoglobin. Hemoglobin and myoglobin illustrate both protein structure–function relationships and the molecular basis of genetic disorders such as sickle cell disease and the thalassemias. Cyanide and carbon monoxide (CO) kill because they disrupt the physiologic function of the heme proteins cytochrome oxidase and hemoglobin, respectively.
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HEME & FERROUS IRON CONFER THE ABILITY TO STORE & TRANSPORT OXYGEN
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Myoglobin and hemoglobin contain heme, an iron-containing cyclic tetrapyrrole consisting of four molecules of pyrrole linked by methyne bridges. This planar network of conjugated double bonds absorbs visible light and colors heme deep red. The substituents at the β-positions of heme are methyl (M), vinyl (V), and propionate (Pr) groups arranged in the order M, V, M, V, M, Pr, Pr, M (Figure 6–1). An atom of ferrous iron (Fe2+) resides at the center of the planar tetrapyrrole. Oxidation of the Fe2+ of myoglobin or hemoglobin to Fe3+ destroys their biologic activity. Other ...