Hemoglobin and Functions of Iron | Patient Education | UCSF Medical Center
Explain the relationship between hemoglobin-oxygen saturation and the partial pressure of oxygen in the blood. What is the functional significance of the shape. Hemoglobin is essential for transferring oxygen in your blood from the lungs to the tissues. Myoglobin, in muscle cells, accepts, stores, transports and releases. Key Concepts: Oxygen Transport in the Blood; Metal Complexes. Ligands; Coordination numbers. Hemoglobin Protein (Interactively view a molecule in this .
The haemoglobin—oxygen dissociation curve describing the relationship between oxygen partial pressure and saturation can be modelled mathematically and routinely obtained clinical data support the accuracy of a historical equation used to describe this relationship. Educational Aims To understand how oxygen is delivered to the tissues. To understand the relationships between oxygen saturation, partial pressure, content and tissue delivery.
The clinical relevance of the haemoglobin—oxygen dissociation curve will be reviewed and we will show how a mathematical model of the curve, derived in the s from limited laboratory data, accurately describes the relationship between oxygen saturation and partial pressure in a large number of routinely obtained clinical samples. To understand the role of pulse oximetry in clinical practice.
To understand the differences between arterial, capillary and venous blood gas samples and the role of their measurement in clinical practice. The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration contentsaturation SO2 and partial pressure, haemoglobin concentration and cardiac output, including its distribution.
Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in Oxygen saturation by pulse oximetry SpO2 is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations.
The use of pulse oximetry reduces the need for arterial blood gas analysis SaO2 as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable SpO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care.
The four heme groups are displayed in the ball-and-stick representation. The coordinates for the hemoglobin protein in this and subsequent molecular representations of all or part of the protein were determined using x-ray crystallography, and the image was rendered using SwissPDB Viewer and POV-Ray see References.
To view the molecule interactively, please use Jmoland click on the button to the left. To understand the oxygen-binding properties of hemoglobin, we will focus briefly on the structure of the protein and the metal complexes embedded in it.
The Protein Subunit Each subunit in Figure 2 contains regions with a coiled shape; many of the amino acids that make up the polypeptide chain interact to form this particular structure, called an alpha helix.
In an alpha helix Figure 3each amino acid is "hydrogen-bonded" to the amino acid that is four residues ahead of it in the chain. In hemoglobin, the hydrogen-bonding interaction occurs between the H of an -NH group and the O of a -CO group of the polypeptide backbone chain; the amino-acid side chains extend outward from the backbone of the helix.
Another common structural motif is the beta-pleated sheet, in which amino acids line up in straight parallel rows. Figure 3 This is a molecular model of the alpha-helix structure in a subunit of hemoglobin. The blue strands are a ribbon representation to emphasize the helical structure.
The green dotted lines show the hydrogen bonding between the -NH and -CO functional groups. To view the molecule interactively, please use Jmoland click on the button above.
Please click on the pink button above to view a QuickTime movie showing a rotation of the alpha-helix structure shown in Figure 3. Click the blue button below to download QuickTime 4. The Heme Group In hemoglobin, each subunit contains a heme group, which is displayed using the ball-and-stick representation in Figure 2.
Each heme group contains an iron atom that is able to bind to one oxygen O2 molecule. Therefore, each hemoglobin protein can bind four oxygen molecules.
Relating oxygen partial pressure, saturation and content: the haemoglobin–oxygen dissociation curve
One of the most important classes of chelating agents in nature are the porphyrins. A porphyrin molecule can coordinate to a metal using the four nitrogen atoms as electron-pair donors, and hence is a polydentate ligand see Figure 1.
Heme is a porphyrin that is coordinated with Fe II and is shown in Figure 4. Figure 4 On the left is a three-dimensional molecular model of heme coordinated to the histidine residue a monodentate ligand, see Figure 1 of the hemoglobin protein. On the right is a two-dimensional drawing of heme coordinated to the histidine residue, which is part of the hemoglobin protein. In this figure, the protein is deoxygenated; i. The coordinate-covalent bonds between the central iron atom and the nitrogens from the porphyrin are gold; the coordinate-covalent bond between the central iron atom and the histidine residue is green.
In the three-dimensional model, the carbon atoms are are gray, the iron atom is dark red, the nitrogen atoms are dark blue, and the oxygen atoms are light red. The rest of the hemoglobin protein is purple. In the body, the iron in the heme is coordinated to the four nitrogen atoms of the porphyrin and also to a nitrogen atom from a histidine residue one of the amino-acid residues in hemoglobin of the hemoglobin protein see Figure 4.
The sixth position coordination site around the iron of the heme is occupied by O2 when the hemoglobin protein is oxygenated. Questions on the Oxygen-Carrying Protein in the Blood: Hemoglobin One peptide subunit in hemoglobin contains amino-acid residues.
If the subunit were stretched out, it would measure approximately 49 nm in length. However, the longest dimension of the subunit in hemoglobin is only about 5 nm. Briefly, explain how alpha helices may help account for this difference in length. What is the coordination number of Fe in the oxygenated heme group?
Metal Complex in the Blood
Briefly, justify your answer by describing the ligands to which Fe is coordinated. Conformational Changes Upon Binding of Oxygen Careful examination of Figure 4 shows that the heme group is nonplanar when it is not bound to oxygen; the iron atom is pulled out of the plane of the porphyrin, toward the histidine residue to which it is attached.
This nonplanar configuration is characteristic of the deoxygenated heme group, and is commonly referred to as a "domed" shape. The valence electrons in the atoms surrounding iron in the heme group and the valence electrons in the histidine residue form "clouds" of electron density.
Electron density refers to the probability of finding an electron in a region of space. Because electrons repel one another, the regions occupied by the valence electrons in the heme group and the histidine residue are pushed apart. Hence, the porphyrin adopts the domed nonplanar configuration and the Fe is out of the plane of the porphyrin ring Figure 5, left. However, when the Fe in the heme group binds to an oxygen molecule, the porphyrin ring adopts a planar configuration and hence the Fe lies in the plane of the porphyrin ring Figure 5, right.
Figure 5 On the left is a schematic diagram showing representations of electron-density clouds of the deoxygenated heme group pink and the attached histidine residue light blue. These regions of electron density push one another apart, and the iron atom in the center is drawn out of the plane.
The nonplanar shape of the heme group is represented by the bent line. On the right is a schematic diagram showing representations of electron-density clouds of the oxygenated heme group pinkthe attached histidine residue light blueand the attached oxygen molecule gray.
The oxygenated heme assumes a planar configuration, and the central iron atom occupies a space in the plane of the heme group depicted by a straight red line. The shape change in the heme group has important implications for the rest of the hemoglobin protein, as well. When the iron atom moves into the porphyrin plane upon oxygenation, the histidine residue to which the iron atom is attached is drawn closer to the heme group. This movement of the histidine residue then shifts the position of other amino acids that are near the histidine Figure 6.
When the amino acids in a protein are shifted in this manner by the oxygenation of one of the heme groups in the proteinthe structure of the interfaces between the four subunits is altered. Hence, when a single heme group in the hemoglobin protein becomes oxygenated, the whole protein changes its shape.
In the new shape, it is easier for the other three heme groups to become oxygenated. Thus, the binding of one molecule of O2 to hemoglobin enhances the ability of hemoglobin to bind more O2 molecules.
This property of hemoglobin is known as "cooperative binding. When hemoglobin is deoxygenated leftthe heme group adopts a domed configuration. When hemoglobin is oxygenated rightthe heme group adopts a planar configuration. As shown in the figure, the conformational change in the heme group causes the protein to change its conformation, as well. Red blood cells are able to carry oxygen so efficiently because of a special protein inside them: In fact, it is the haemoglobin that is responsible for the colour of the red blood cell.
Haemoglobin contains a haem prosthetic group that has an iron atom at its centre. When the iron is bound to oxygen, the haem group is red in colour oxyhameoglobinand when it lacks oxygen deoxygenated form it is blue-red. As blood passes through the lungs, the haemoglobin picks up oxygen because of the increased oxygen pressure in the capillaries of the lungs, and can then release this oxygen to body cells where the oxygen pressure in the tissues is lower.
In addition, the red blood cells can pick up the waste product, carbon dioxide, some of which is carried by the haemoglobin at a different site from where it carries the oxygenwhile the rest is dissolved in the plasma. The high carbon dioxide levels in the tissues lowers the pH, and the binding of haemoglobin to carbon dioxide causes a conformational change that facilitates the release of oxygen.
The carbon dioxide is then released once the red blood cells reach the lungs. Haemoglobin is composed of four polypeptide chains, which in adults consist of two alpha a globin chains and two beta b globin chains i.
Each polypeptide has a haem prosthetic group attached, where each haem can bind one oxygen molecule - so there are four haem groups per haemoglobin molecule that together bind four oxygen molecules.