hemoglobin(redirected from Glycated hemoglobin)
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hemoglobin(hē`məglō'bĭn), respiratory protein found in the red bloodblood,
fluid pumped by the heart that circulates throughout the body via the arteries, veins, and capillaries (see circulatory system; heart). An adult male of average size normally has about 6 quarts (5.6 liters) of blood.
..... Click the link for more information. cells (erythrocytes) of all vertebrates and some invertebrates. A hemoglobin molecule is composed of a protein group, known as globin, and four heme groups, each associated with an iron atom.
In the lungs, each iron atom combines reversibly with a molecule of oxygen. Each hemoglobin molecule also has attached a single cysteine amino acid, which attracts nitric oxide from the lungs. The enriched hemoglobin circulates and is carried through the body to the tissues, where the nitric oxide dilates the small capillaries, allowing hemoglobin to deliver its oxygen to the tissues. Then the oxygen- and nitric oxide–free hemoglobin molecule picks up carbon dioxide and free nitric oxide and transports both back to the lungs, where they are exhaled as waste.
Hemoglobin is produced in bone marrowbone marrow,
soft tissue filling the spongy interiors of animal bones. Red marrow is the principal organ that forms blood cells in mammals, including humans (see blood). In children, the bones contain only red marrow.
..... Click the link for more information. by erythrocytes and is circulated with them until their destruction. It is then broken down in the spleen, and some of its components, such as iron, are recycled to the bone marrow. Other components, such as the heme groups, are broken down into bilirubin, transported to the liver, and secreted with the bilebile,
bitter alkaline fluid of a yellow, brown, or green color, secreted, in man, by the liver. Bile, or gall, is composed of water, bile acids and their salts, bile pigments, cholesterol, fatty acids, and inorganic salts.
..... Click the link for more information. into the intestine for eventual elimination from the body.
Hemoglobin deficiency may be a result of structural abnormality in the hemoglobin molecules themselves. In sickle cell diseasesickle cell disease
or sickle cell anemia,
inherited disorder of the blood in which the oxygen-carrying hemoglobin pigment in erythrocytes (red blood cells) is abnormal.
..... Click the link for more information. , this structural abnormality creates malformed red blood cells which clog blood vessels, severely restricting the supply of blood flowing to body tissues.
The oxygen-carrying molecule of the red blood cells of vertebrates. This protein represents more than 95% of the solid constituents of the red cell. It is responsible for the transport of oxygen from the lungs to the other tissues of the body and participates in the transport of carbon dioxide in the reverse direction.
Each molecule of hemoglobin comprises four smaller subunits, called polypeptide chains. These are the protein or globin parts of hemoglobin. A heme group, which is an iron-protoporphyrin complex, is associated with each polypeptide subunit and is responsible for the reversible binding of one molecule of oxygen. The polypeptide chains and the heme are synthesized and combine together in nucleated red cells of the bone marrow. As these cells mature, the nuclei fragment and the cells, now called reticulocytes, begin to circulate in the blood. After sufficient hemoglobin has been formed in the reticulocyte, all nuclear material disappears and the cell is then called an erythrocyte, or red blood cell. Each hemoglobin molecule lasts as long as the red cell, which has an average life of 120 days. See Porphyrin
Normal adult males and females have about 16 and 14 g, respectively, of hemoglobin per 100 ml of blood; each red cell contains about 29 × 10-12 g of hemoglobin. Red cells normally comprise 40–45% of the volume of whole blood.
The reversible combination of hemoglobin and oxygen can be represented by the reaction shown below. The equilibrium constants for each step are not the same because an oxygen molecule on one heme group changes the affinity of the other hemes for additional oxygen molecules. This alteration in binding affinity during oxygenation is called heme-heme interaction and is due to small changes in the three-dimensional structure of the molecule.
Hemoglobin combines reversibly with carbon monoxide about 210 times more strongly than with oxygen. This strong affinity for carbon monoxide accounts for the poisoning effects of this gas.
Hemoglobin binds carbon dioxide by means of free amino groups of the protein but not by the heme group. The reversible combination with carbon dioxide provides part of the normal blood transport of this gas. Hemoglobin serves also as a buffer by reversible reactions with hydrogen ions. The acidic property of oxyhemoglobin is greater than deoxygenated hemoglobin. The extra binding of hydrogen ion by deoxyhemoglobin promotes the conversion of tissue carbon dioxide into bicarbonate ion and thus increases the amount of total carbon dioxide which can be transported by blood. See Blood, Respiration
(Hb), a red iron-containing pigment in the blood of man, vertebrates, and some invertebrates.
The function of hemoglobin in the organism is the transport of oxygen (02) from the respiratory organs to the tissues; it also plays an important role in transporting gaseous carbon dioxide from the tissues to the respiratory organs. In most invertebrates hemoglobin is freely dissolved in the blood; in vertebrates and some invertebrates, it is present in the red blood cells (erythrocytes), constituting about 94 percent of their dry weight. The molecular weight of erythrocytic hemoglobin is about 66,000; the weight of the hemoglobin dissolved in plasma may be as much as 3,000,000. Chemically, hemoglobin is a complex chromoprotein consisting of the protein globin and the ferroporphyrin heme. In higher animals and man, hemoglobin consists of four subunits, or monomers, each with a molecular weight of about 17,000. Two of the monomers (alpha chains) contain 141 amino acid residues each; each of the other two (beta chains) contains 146 residues.
The spatial structures of these polypeptides are similar in many respects. They form characteristic “hydrophobic pockets” containing one heme molecule per subunit. Of the six coordinate bonds of the iron atom in heme, four are directed toward the nitrogen of the pyrrole rings; the fifth is connected to the nitrogen of the imidazole ring of histidine, a polypeptide that stands in the 87th position in the alpha polypeptide chain and 92nd in the beta chain; the sixth bond is directed toward a water molecule or other groups (ligands), including oxygen. The subunits are loosely bound to one another by hydrogen, salt links, and other noncovalent bonds, and they readily dissociate under the influence of amides and high salt concentrations, mostly to form symmetrical dimers (αβ) and partly to form alpha and beta monomers. The spatial structure of the hemoglobin molecule has been studied by X-ray diffraction analysis (M. Perutz, 1959).
The sequential positions of the amino acids in the alpha and beta chains of hemoglobin in a number of higher animals and man have been completely ascertained. In the tetrameric hemoglobin molecule all four heme residues are located on the surface and readily accessible to reaction with O2. Oxygenation is ensured by the presence of the Fe2+ atom in heme. This reaction is reversible and depends upon the partial pressure (tension) of O2. Hemoglobin combines with O2 to form oxyhemoglobin (oxygenation) in the capillaries of the lungs, where O2 tension is about 100 millimeters of mercury (mm Hg). Oxyhemoglobin dissociates to hemoglobin and O2 in the capillaries of tissues, where O2 tension is much lower (about 40 mm Hg). The freed oxygen enters the cells of organs and tissues, where the partial pressure of O2 is still lower (5-20 mm Hg, within the cell diminishing almost to zero). The union of O2 with hemoglobin and the dissociation of oxyhemoglobin to hemoglobin and O2 are accompanied by changes in conformation of the hemoglobin molecule and by reversible breakdown into dimers and monomers, followed by aggregation into tetramers. (See Figure 1.)
Other properties of hemoglobin also change upon reaction with 02; oxygenated hemoglobin is an acid 70 times stronger than hemoglobin. This plays an important part in the binding of C02 in the tissues and its release in the lungs. Absorption bands in the visible part of the spectrum are characteristic: hemoglobin has a single maximum at 554 millimicrons (mμ) and oxygenated hemoglobin has two maxima (at 578 and 540 mμ). Hemoglobin can combine directly with C02 (as a result, of reaction with the NH2 groups of globin) to form carbamino hemoglobin, an unstable compound that readily breaks down in the capillaries of the lung into hemoglobin and CO2.
The amount of hemoglobin in human blood averages 13-16 gram percent (or 78-96 percent according to Sahli); females have somewhat less hemoglobin than males. The properties of hemoglobin change in the course of the organism’s development. The hemoglobin is therefore defined as either fetal (HbF) or adult (HbA). Fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin, a fact of great physiological significance in that it ensures greater stability in the fetal stage in cases of O2 insufficiency. The determination of the amount of hemoglobin in the blood is important in characterizing the respiratory functions of the blood, both under normal conditions and in a great variety of diseases (especially in diseases of the blood). The amount of hemoglobin is determined by special devices called hemoglo-binometers.
In certain diseases and in congenital blood abnormalities (hemoglobinopathies), anomalous (pathological) hemoglobins appear in the red blood cells. These hemoglobins differ from the normal in the substitution of an amino acid residue in the alpha or beta chains. More than 50 kinds of anomalous hemoglobins have been identified. Sickle-cell anemia, for example, is characterized by the presence of hemoglobin in whose beta chains glutamic acid, which stands in the sixth position from the N-(amino-) terminus, is replaced by valine. Erythrocytic anomalies associated with hemoglobin F or hemoglobin H underlie the conditions of thalassemia and methemoglobinemia. The respiratory function of certain anomalous hemoglobins is severely impaired, giving rise to various pathological conditions (for example, anemias). The properties of hemoglobin may be altered by poisoning. Carbon monoxide, for example, stimulates the formation of car-boxyhemoglobin; other poisons may change the Fe2+ of heme into Fe3+, with the formation of methemoglobin. These hemoglobin derivatives are incapable of oxygen transport. The hemoglobins of various animals are species-specific because of the peculiar structure of the protein part of the molecule. The hemoglobin liberated upon the destruction of erythrocytes is utilized to form bile pigments.
Muscle tissue contains muscle hemoglobin (myoglobin), which is similar in molecular weight, composition, and properties to the subunits (monomers) of hemoglobin. Analogues of hemoglobin have been found in certain plants (for example, leghemoglobin, found in leguminous root nodules).
REFERENCESKorzhuev, P. A. Gemoglobin. Moscow, 1964.
Haurowitz, F. Khimiia i funktsii belkov, 2nd ed. Moscow, 1965. Pages 303-23. (Translated from English.)
Ingram, V. Biosintez makromolekul. Moscow, 1966. Pages 188-97. (Translated from English.)
Rapoport, S. M. Meditsinskaia biokhimiia. Moscow, 1966. (Translated from German.)
Perutz, M. “Molekula gemoglobina.” In the collection Molekuly i kletki. Moscow, 1966. (Translated from English.)
Zuckerkandl, E. “Evoliutsiia gemoglobina.” In the collection Molekuly i kletki. Moscow, 1966.
Fanelli, A. R., E. Antonini, and A. Caputo. “Hemoglobin and Myoglobin.” Advances in Protein Chemistry, 1964, vol. 19, pp. 73-222.
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G. V. ANDREENKO and S. E. SEVERIN