Hemoglobin

Hemoglobin or haemoglobin (frequently abbreviated as Hb, {{PDB|1A3N}}) is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. The molecule consists of globin, the apoprotein, and four heme (or haem) groups, which are organic molecules with an iron atom in each.

Binding of ligands

In the tetrameric form of normal adult hemoglobin, the binding of oxygen is a cooperative process. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule. As a consequence, the oxygen binding curve of hemoglobin is sigmoidal, or 'S' shaped, as opposed to the normal hyperbolic (noncooperative) curve. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex: when one subunit protein in hemoglobin becomes oxygenated it induces a confirmation or structural arrangement change in the whole complex causing the other 3 subunits to gain an increased affinity for oxygen.

Related Topics:
Cooperative - Steric

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Hemoglobin's affinity for oxygen is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin, carbon monoxide binding preferentially to oxygen. Carbon dioxide occupies a different binding site on the hemoglobin. Carbon dioxide reacts with water to give bicarbonate, carbonic acid freed protons via the reaction, which is catalyzed by carbonic anhydrase:

Related Topics:
Carbon monoxide - Bicarbonate - Carbonic acid - Carbonic anhydrase

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:CO2 + H2O HCO3- + H+

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So blood with high carbon dioxide levels is also lower in pH (more acidic). Hemoglobin can bind protons and carbon dioxide which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places along the protein and carbon dioxide binds at the alpha-amino group forming carbamate. Conversely, when the carbon dioxide levels in the blood decrease (i.e. around the lungs), carbon dioxide is released, increasing the oxygen affinity of the protein. This control of hemoglobin's affinity for oxygen by the binding and release of carbon dioxide is known as the Bohr effect.

Related Topics:
PH - Acidic - Proton - Alpha-amino group - Carbamate - Bohr effect

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The binding of oxygen is affected by molecules such as carbon monoxide (CO) (For example from tobacco smoking, cars and furnaces). CO competes with oxygen at the heme binding site. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduces hemoglobin?s ability to transport oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin. When inspired air contains CO levels as low as 0.02% headache and nausea occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen active sites can be blocked by CO.

Related Topics:
Carbon monoxide - Tobacco smoking

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Hemoglobin also has competitive binding affinity for Sulfur monoxide (SO), Nitrogen Dioxide (NO2) and Hydrogen sulfide (H2S). The iron atom in the heme group must be in the Fe+2 oxidation state to support oxygen transport. Oxidation to Fe+3 state converts hemoglobin into hemiglobin or methemoglobin which cannot bind oxygen. Nitrogen dioxide and nitrous oxide are capable of converting hemoglobin to methemoglobin.

Related Topics:
Sulfur monoxide - Nitrogen Dioxide - Hydrogen sulfide - Methemoglobin - Nitrous oxide

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In people acclimated to high altitudes, the concentration of 2,3-diphosphoglycerate (2,3-DPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension. This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect.

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A variant hemoglobin, called fetal hemoglobin (Hb F, α2γ2), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. Consequently, the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension) in comparison to that of adult hemoglobin.

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