9.2 Myoglobin and Hemoglobin Bind Oxygen in Heme Groups

Figure 9.3: The structure of myoglobin. Notice that myoglobin consists of a single polypeptide chain, formed of helices connected by turns, with one oxygen-binding site.

Myoglobin, a single polypeptide chain, consists largely of a helices that are linked to one another by turns in the polypeptide chain to form a globular structure (Figure 9.3). The recurring structure is called a globin fold and is also seen in hemoglobin.

Myoglobin can exist in either of two forms: as deoxymyoglobin, an oxygen-free form, or as oxymyoglobin, a form having a bound oxygen molecule. The ability of myoglobin, as well as that of hemoglobin, to bind oxygen depends on the presence of a bound prosthetic group called heme.

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The heme group gives muscle and blood their distinctive red color. It consists of an organic component and a central iron atom. The organic component, called protoporphyrin, is made up of four pyrrole rings linked by methine bridges to form a tetrapyrrole ring. Four methyl groups, two vinyl groups, and two propionate side chains are attached.

The iron atom lies in the center of the protoporphyrin, bonded to the four pyrrole nitrogen atoms. Under normal conditions, the iron is in the ferrous (Fe2+) oxidation state. The iron ion can form two additional bonds, one on each side of the heme plane. These binding sites are called the fifth and sixth coordination sites. In hemoglobin and myoglobin, the fifth coordination site is occupied by the imidazole ring of a histidine residue of the protein. This histidine residue is referred to as the proximal histidine. In deoxyhemoglobin and deoxymyoglobin, the sixth coordination site remains unoccupied; this position is available for binding oxygen. The iron ion lies approximately 0.4 Å outside the porphyrin plane because an iron ion, in this form, is slightly too large to fit into the well-defined hole within the porphyrin ring (Figure 9.4, left). A second histidine, called the distal histidine, resides on the opposite side of the heme from the proximal histidine. The distal histidine prevents the oxidation of the heme iron to the ferric ion (Fe3+), which cannot bind oxygen, and also reduces the ability of carbon monoxide to bind to the heme (problem 22).

Figure 9.4: Oxygen binding changes the position of the iron ion. The iron ion lies slightly outside the plane of the porphyrin in deoxyhemoglobin heme (left) but moves into the plane of the heme on oxygenation (right).

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The binding of the oxygen molecule at the sixth coordination site of the iron ion substantially rearranges the electrons within the iron so that the ion becomes effectively smaller, allowing it to move into the plane of the porphyrin (Figure 9.4, right). The bound oxygen is stabilized by forming a hydrogen bond with the distal histidine.

Figure 9.5: Brain response to odorants. A functional magnetic resonance image reveals brain response to odorants. The light spots indicate regions of the brain activated by odorants.

!clinic! CLINICAL INSIGHT: Functional Magnetic Resonance Imaging Reveals Regions of the Brain Processing Sensory Information

The change in electronic structure that takes place when the iron ion moves into the plane of the porphyrin is paralleled by changes in the magnetic properties of hemoglobin; these changes are the basis for functional magnetic resonance imaging (fMRI), one of the most powerful methods for examining brain function. Nuclear magnetic resonance techniques detect signals that originate primarily from the protons in water molecules but are altered by the magnetic properties of hemoglobin. With the use of appropriate techniques, images can be generated that reveal differences in the relative amounts of deoxy- and oxyhemoglobin and thus the relative activity of various parts of the brain. When a specific part of the brain is active, blood vessels relax to allow more blood flow to the active region. Thus, a more active region of the brain will be richer in oxyhemoglobin.

These noninvasive methods reveal areas of the brain that process sensory information. For example, subjects have been imaged while breathing air that either does or does not contain odorants. When odorants are present, the fMRI technique detects an increase in the level of hemoglobin oxygenation (and, hence, brain activity) in several regions of the brain (Figure 9.5). Such regions include those in the primary olfactory cortex as well as other regions in which secondary processing of olfactory signals presumably takes place. Further analysis reveals the time course of activation of particular regions and other features. Functional MRI shows tremendous potential for mapping regions and pathways engaged in processing sensory information obtained from all the senses. Thus, a seemingly incidental aspect of the biochemistry of hemoglobin has yielded the basis for observing the brain in action.