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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 that its O2-binding curve be sigmoidal rather than hyperbolic.
  • Explain the role of a hindered environment on the ability of hemoglobin to bind carbon monoxide.
  • 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.
  • Outline the role of hemoglobin in CO2 and proton transport, and describe accompanying changes in the pKa of the relevant imidazolium group.
  • Describe the structural consequences to HbS of lowering pO2.
  • Identify the metabolic defect that occurs as a consequence of α- and -β thalassemias.


The heme proteins myoglobin and hemoglobin maintain a supply of oxygen essential for oxidative metabolism. Myoglobin, a monomeric protein of red muscle, stores oxygen as a reserve against oxygen deprivation. Hemoglobin, a tetrameric protein of erythrocytes, transports O2 to the tissues and returns CO2 and protons to the lungs. Cyanide and carbon monoxide kill because they disrupt the physiologic function of the heme proteins cytochrome oxidase and hemoglobin, respectively. The secondary-tertiary structure of the subunits of hemoglobin resembles myoglobin. However, the tetrameric structure of hemoglobin permits cooperative interactions that are central to its function. For example, 2,3-BPG promotes the efficient release of O2 by stabilizing the quaternary structure of deoxyhemoglobin. Hemoglobin and myoglobin illustrate both protein structure–function relationships and the molecular basis of genetic diseases such as sickle cell disease and the thalassemias.


Myoglobin and hemoglobin contain heme, a 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). The atom of ferrous iron (Fe2+) resides at the center of the planar tetrapyrrole. Other proteins with metal-containing tetrapyrrole prosthetic groups include the cytochromes (Fe and Cu) and chlorophyll (Mg) (see Chapter 31). Oxidation and reduction of the Fe and Cu atoms of cytochromes are essential to their biologic function as carriers of electrons. By contrast, oxidation of the Fe2+ of myoglobin or hemoglobin to Fe3+ destroys their biologic activity.

Figure 6–1
Graphic Jump Location

Heme. The pyrrole rings and methyne bridge carbons are coplanar, and the iron atom (Fe2+) resides in almost the same plane. The ...

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