Academic literature on the topic 'Diphosphoglycerate'

Numerous enzymes, including those of the hexose monophosphate pathway and glycolysis, are active in the red cell. They are required for the generation of ATP (needed to supply energy for sodium extrusion) and the reductants NADH and NADPH, necessary to maintain haemoglobin in its active ferrous atomic state, as well as for the integrity of sulphydryl groups present on essential proteins. 2,3-diphosphoglycerate (2,3-DPG), an intermediate of ...

Ascent to altitudes above 2500 m leads to exposure to hypobaric hypoxia. This affects performance on first arrival at high altitude and disturbs sleep, but physiological changes occur over time to defend arterial and tissue oxygenation and allow the individual to adjust. This process of acclimatization includes (1) an increase in the rate and depth of breathing; and (2) an increase in red cell mass, and in red cell 2,3-diphosphoglycerate. Acclimatization is no longer possible at extreme altitude (>5800 m) and the exposed individual will gradually deteriorate....

Ascent to altitudes above 2,500 m leads to exposure to hypobaric hypoxia. This affects performance on first arrival at high altitude and disturbs sleep, but physiological changes occur over time to defend arterial and tissue oxygenation and allow the individual to adjust. This process of acclimatization includes (1) an increase in the rate and depth of breathing; and (2) an increase in red cell mass, and in red cell 2,3-diphosphoglycerate. Acclimatization is no longer possible at extreme altitude (>5,800 m) and the exposed individual will gradually deteriorate. Altitude illness results from a failure to adjust to hypobaric hypoxia at altitude. Risk is increased by ascent to higher altitudes, by more rapid gain in altitude, and (in some people) genetic predisposition; the condition may be avoided in most cases by slow, graded ascent.

Numerous enzymes, including those of the hexose monophosphate and glycolytic pathways, are active in the red cell. They are required for the generation of ATP and the reductants NADH and NADPH. 2,3-Diphosphoglycerate, an intermediate of glucose metabolism, is a key regulator of the affinity of haemoglobin for oxygen, and accessory enzymes are also active for the synthesis of glutathione, disposal of oxygen free radicals, and for nucleotide metabolism. With the exception of heavy metal poisoning and rare cases of myelodysplasia, most red cell enzyme deficiency disorders are inherited. They may cause haematological abnormalities, (most commonly nonspherocytic haemolytic anaemias, but also rarely polycythaemia or methaemoglobinaemia, manifest with autosomal recessive or sex-linked inheritance), and may also be associated with nonhaematological disease when the defective enzyme is expressed throughout the body. Some may mirror important metabolic disorders, without producing haematological problems, making them of diagnostic value. Others are of no known clinical consequence. With rare exceptions, it is impossible to differentiate the enzymatic defects from one another by clinical or routine laboratory methods. Diagnosis depends on the combination of (1) accurate ascertainment of the family history; (2) morphological observations—these can determine whether haemolysis is present, rule out some causes of haemolysis (e.g. hereditary spherocytosis and other red blood cell membrane disorders), and diagnose pyrimidine 5′-nucleotidase deficiency (prominent red cell stippling); (3) estimation of red cell enzyme activity; and (4) molecular analysis. The most common red cell enzyme defects are glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, glucose-6-phosphate isomerase deficiency, pyrimidine 5′-nucleotidase deficiency—which may also induced by exposure to environmental lead—and triosephosphate isomerase deficiency.

Human normal adult hemoglobin (Hb) A, the oxygen carrier of blood, is a tetrameric protein consisting of two α chains of 141 amino acid residues each and two β chains of 146 amino acid residues each. Each Hb chain contains a heme group which is an iron complex of protoporphyrin IX. Under physiological conditions, the heme-iron atoms of Hb remain in the ferrous state. In the absence of oxygen, the four heme-irom atoms in Hb A are in the highspin ferrous state [Fe(II)] with four unpaired electrons each. Each of the four heme-iron atoms in Hb A can combine with an O2 molecule to give oxyhemoglobin (HbO2) in which the iron atom is in a low-spin, diamagnetic ferrous state. The oxygen binding of Hb exhibits sigmoidal behavior, with an overall association constant expression giving a greater than first-power dependence on the concentration of O2. Thus, the oxygenation of Hb is a cooperative process, such that when one O2 is bound, succeeding O2 molecules are bound more readily. Hb is an allosteric protein, i.e., its functional properties are regulated by a number of metabolites [such as hydrogen ions, chloride, carbon dioxide, 2,3-diphosphoglycerate (2,3-DPG)] other than its ligand, O2. It has been used as a model for allosteric proteins, and indeed, hemoglobins of vertebrates are among the most extensively studied allosteric proteins. Their allosteric properties are physiologically important in optimizing O2 transport by erythrocytes. The large number of mutant forms of Hb available provides an array of structural alterations with which to correlate effects on function. For details, see DickersonandGeis (1983), Bunnand Forget (1986), Ho (1992), Ho and Perussi (1994). There are two types of contacts between the α and β subunits of Hb (Perutz, 1970; Dickerson and Geis, 1983). The α1β1 (or α2 β2) contacts, involving B, G, and H helices, and GH corners, are called packing contacts. These contacts remain unchanged and hold the dimer together even when there is a change in the ligation state of the heme.