How many binding sites does hemoglobin have

Hemoglobin is definitely not a pure two-state system, but the T to R transition provides the major, first-level explanation of its function.

They are different but homologous, with a "globin fold" structure similar to myoglobin. Here we see a single of hemoglobin, starting with an overview of the subunit. The helices form an approximately-cylindrical bundle, with the heme and its central Fe atom bound in a. The heme is quite domed in the deepskyblue T-state deoxy form , with the 5-coordinate, high-spin Fe orange ball out of the plane. In the pink R-state form a CO molecule is bound at the right C in green , O in red ; the Fe, now 6-coordinate low-spin, has moved into the heme plane, which has flattenened.

The proximal His at left connects the Fe to helices on the proximal side, making the Fe position sensitive to changes in the globin structure and vice versa. Remember that this scene shows a subunit in the all-unliganded versus the all-liganded states of Hb; when oxygen binds to just one subunit, then its internal structure undergoes some but not all of these changes, depending on conditions.

O 2 binds in the same place as CO, with similar effects on the structure; however, for O2 the outer atom is angled rather than straight. The equilibrium between free and bound O 2 is very rapid, with on and off rates that are sensitive to protein conformation. Both CO and NO dissociate from the Fe atom very slowly, so that these gases act as respiratory poisons.

The heme is surrounded by a hydrophobic pocket, which is necessary in order for it to bind oxygen reversibly without undergoing oxidation or other undesirable reactions.

The heme binding pocket contains mostly , shown in grey. They actually surround the binding site so thoroughly that O2 cannot get in or out without parts of the protein moving out of the way a bit, so that its dynamic properties are essential to have any O2 binding at all; this restrictive process also increases the specificity of ligand binding.

These monomers bind O2 quite tightly, which would work well for loading O2 in the lungs but would not allow unloading it for delivery to the tissues. Therefore, the central critical feature of hemoglobin function is how it achieves, uses, and allosterically controls cooperativity between the 4 binding sites in the tetramer to tune O2 binding for satisfying physiological needs. Linkage of the heme Fe through the proximal His results in tertiary-structure changes that can then transmit their effects to other subunits in the tetrameric assemblage.

This allows O2 binding in one subunit to indirectly affect the affinitiy of other subunits. The influence of one oxygen's binding on the binding of another oxygen is called a homotropic effect. Overall, this cooperative equilibrium binding makes the binding curve sigmoidal rather than hyperbolic, as Figure shows. The P 50 of hemoglobin in red blood cells is about 26 torr under normal physiological conditions.

In the alveoli of the lungs, pO 2 is about torr, and close to 20 torr in the tissues. Figure 3. Cooperativity is a complex subject; one model is the interconversion of the hemoglobin between two states—the T tense and the R relaxed conformations—of the molecule. The R state has higher affinity for oxygen. Under conditions where pO 2 is high such as in the lungs , the R state is favored; in conditions where pO 2 is low as in exercising muscle , the T state is favored. Quantitatively, the binding curve of a complex protein like hemoglobin is described by the approximation:.

The equation can be manipulated into logarithmic form:. A graph of this equation yields a Hill plot named after the British physiologist who first described it , as shown in Figure.

For myoglobin, which only has one subunit, the slope must be 1; for hemoglobin, the Hill coefficient is 2. The blood distributes oxygen and nutrients to the many different cells in the body, carries CO 2 generated by the cells to the lungs for exhalation, and carries other waste products to the kidneys and liver for processing and elimination. Many finely tuned chemical processes occur in the blood to allow the blood to carry out all of these functions and provide for the needs of the body.

In this tutorial, we will study one of the most important functions of blood, the transport of oxygen from the lungs to the other cells of the body e. An adult at rest consumes the equivalent of ml of pure oxygen per minute. This oxygen is used to provide energy for all the tissues and organs of the body, even when the body is at rest. The body's oxygen needs increase dramatically during exercise or other strenuous activities.

The oxygen is carried in the blood from the lungs to the tissues where it is consumed. However, only about 1. Transporting the large amount of oxygen required by the body, and allowing it to leave the blood when it reaches the tissues that demand the most oxygen, require a more sophisticated mechanism than simply dissolving the gas in the blood.

To meet this challenge, the body is equipped with a finely-tuned transport system that centers on the metal complex heme. The ability of metal ions to coordinate with bind and then release ligands in some processes, and to oxidize and reduce in other processes makes them ideal for use in biological systems. The most common metal used in the body is iron, and it plays a central role in almost all living cells.

For example, iron complexes are used in the transport of oxygen in the blood and tissues. Metal-ion complexes consist of a metal ion that is bonded via "coordinate-covalent bonds" Figure 1 to a small number of anions or neutral molecules called ligands.

For example the ammonia NH 3 ligand used in this experiment is a monodentate ligand; i. Some ligands have two or more electron-pair-donor atoms that can simultaneously coordinate to a metal ion and occupy two or more coordination sites; these ligands are called polydentate ligands.

They are also known as chelating agents from the Greek word meaning "claw" , because they appear to grasp the metal ion between two or more electron-pair-donor atoms. The coordination number for a metal refers to the total number of occupied coordination sites around the central metal ion i. You have already learned that a covalent bond forms when electrons are shared between atoms. A coordinate-covalent bond represented by a green arrow in this diagram forms when both of the shared electrons come from the same atom, called the donor atom blue.

An anion or molecule containing the donor atom is known as a ligand. The top illustration shows a coordinate-covalent bond between a metal ion e. The bottom illustration shows a metal ion with coordinate-covalent bonds to a bidentate ligand a ligand that contains two donor atoms simultaneously coordinated to the metal ion, shown in yellow. Hemoglobin is the protein that transports oxygen O 2 in human blood from the lungs to the tissues of the body. Proteins are formed by the linking of amino acids into polypeptide chains.

An individual amino acid in a protein is known as a "residue. Hemoglobin is a globular protein i. Each protein subunit is an individual molecule that joins to its neighboring subunits through intermolecular interactions. These subunits are also known as peptide chains. You will learn more about the nature of amino acids and peptide subunits in the tutorial entitled, " Iron Use and Storage in the Body: Ferritin and Molecular Representations ". This is a molecular model of hemoglobin with the subunits displayed in the ribbon representation.

A ribbon representation traces the backbone atoms of a protein and is often used to represent its three-dimensional structure. The four heme groups are displayed in the ball-and-stick representation. Note: 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.

Note: To view the molecule interactively, please use Jmol , and 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. 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 3 , each 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. This is a molecular model of the alpha-helix structure in a subunit of hemoglobin. The hemes are much too far apart to interact directly. But, changes that occur in the structure of the globin that surrounds a heme when it picks up an O 2 molecule are mechanically transmitted to the other globins in this protein.

These changes carry the signal that facilitates the gain or loss of an O 2 molecule by the other hemes. Drawings of the structures of proteins often convey the impression of a fixed, rigid structure, in which the side-chains of individual amino acid residues are locked into position.

Nothing could be further from the truth. The changes that occur in the structure of hemoglobin when oxygen binds to the hemes are so large that crystals of deoxygenated hemoglobin shatter when exposed to oxygen.