Heme: is formed when iron is inserted into the chemical compound protoporphyrin
Hemin: normal heme contains iron in the ferrous oxidation state (Fe2+), whereas hemin contains iron in the ferric oxidation state (Fe3+)
Methemoglobin: the form of the hemoglobin protein that contains ferric iron (Fe3+) in the heme prosthetic groups due to oxidation
Hemoglobinopathy: any disease resulting from either (or both) quantitative or qualitative defects in α-globin or β-globin proteins
Thalassemia: specifically refers to quantitative hemoglobinopathies due to either α-globin or β-globin protein defects
Sickle cell anemia: most commonly occurring qualitative hemoglobinopathy, results from a single amino acid substitution in the adult β-globin gene
Cooley anemia: is thalassemia major, which is either β0− and β+-thalassemia
Myoglobin and hemoglobin are hemeproteins whose physiological importance is principally related to their ability to bind molecular oxygen. Hemoglobin is a heterotetrameric oxygen transport protein found in red blood cells (erythrocytes), whereas myoglobin is a monomeric protein found mainly in muscle tissue where it serves as an intracellular storage site for oxygen. The oxygen carried by hemeproteins such as hemoglobin and myoglobin is bound directly to the ferrous iron (Fe2+) atom of the heme prosthetic group. Oxidation of the iron to the ferric (Fe3+) state renders the molecule incapable of normal oxygen binding. When the iron in heme is in the ferric state, the molecule is referred to as hemin.
The tertiary structure of myoglobin is that of a typical water-soluble globular protein. Its secondary structure is unusual in which it contains a very high proportion (75%) of α-helical secondary structure. Each myoglobin molecule contains a single heme group inserted into a hydrophobic cleft in the protein. Hydrophobic interactions between the tetrapyrrole ring and hydrophobic amino acid R groups on the interior of the cleft in the protein strongly stabilize the heme–protein conjugate. In addition, a nitrogen atom from a histidine R group located above the plane of the heme ring is coordinated with the iron atom further stabilizing the interaction between the heme and the protein. In oxymyoglobin the remaining bonding site on the iron atom (the 6th coordinate position) is occupied by the oxygen, whose binding is stabilized by a second histidine residue.
Adult hemoglobin is a heterotetrameric [α(2):β(2)] hemeprotein (Figure 6-1) found in erythrocytes where it is responsible for binding oxygen in the lung and transporting the bound oxygen throughout the body, where it is used in aerobic metabolic pathways. Each subunit of a hemoglobin tetramer has a heme prosthetic group identical to that described for myoglobin. The quaternary structure of hemoglobin leads to physiologically important allosteric interactions between the subunits, a property lacking in monomeric myoglobin, which is otherwise very similar to the α-subunit of hemoglobin.
Hemoglobin. Shown is the three-dimensional structure ...