Haemoglobin is one of the most important molecules in the animal kingdom. Its function is to carry oxygen to tissues. In lower invertebrates the blood pigment is present in the haemolymph and is not bound in cells. Later in the course of phylo genesis haemoglobin remains associated with cells which produce it and in this form it reaches the peripheral circulation. In higher organisms the haemoglobin production is thus determined by two main factors: haemoglobin synthesis in erythroid cells and the formation of these erythroid cells which depends on cell proliferation in haematopoietic organs.…mehr
Haemoglobin is one of the most important molecules in the animal kingdom. Its function is to carry oxygen to tissues. In lower invertebrates the blood pigment is present in the haemolymph and is not bound in cells. Later in the course of phylo genesis haemoglobin remains associated with cells which produce it and in this form it reaches the peripheral circulation. In higher organisms the haemoglobin production is thus determined by two main factors: haemoglobin synthesis in erythroid cells and the formation of these erythroid cells which depends on cell proliferation in haematopoietic organs. Human haemoglobin is made up of two chains which combine from four different polypeptide chains formed in varying ratios in different periods of the life cycle. During the life span of humans the following haemoglobins are formed: embryonic haemoglobins Gower 1 and 2, foetal haemoglobin F and two adult haemoglobins A and A . E-and IX-chains are part of the embryonic haemoglobins Gower 1 (E4)and 2 Gower 2 (1X2E2). These haemoglobins predominate in embryos during the second month of pregnancy and at the end of the first trimester they are completely re placed by foetal haemoglobin F (~Y2). Adult haemoglobin A consists of two IX and two ~-chains and is the main component of red cells in adults. A relatively small component of red cells accounting for less than 2 % of the total haemo globin, is haemoglobin A2 (1X0).
1. Introduction.- 2. Substrate Supply for Haemoglobin Syntheses.- Iron Uptake.- Mechanism of iron supply to erythroid cells.- Factors influencing iron uptake by erythroid cells.- Iron and transferrin levels and transferrin saturation.- Metabolic state of crythroid cells.- The role of sulfhydryl groups in iron uptake.- Other factors which influence iron uptake.- Iron uptake from chelating agents.- Intracellular kinetics of iron.- Ferritin.- Other non-haem iron proteins and iron complexes.- Mitochondrial iron.- Inhibitors of haem synthesis as a tool in investigations of the intracellular kinetics of iron.- Regulation of iron supply for haemoglobin synthesis.- Effect of haem on iron uptake by reticulocytes.- Effort of inhibitors of haem and globin syntheses on iron uptake.- Mechanism of the effcct of haem on iron uptake.- Regulation of Uptake of Glycine and other Amino Acids.- 3. Haem Synthesis.- Biosynthesis of Haem.- General introduction.- ALA synthesis.- ALA synthetase.- Porphobilinogen (PBG) synthesis. ALA dehydrase enzyme.- Conversion of porphobilinogen (PBG) to uroporphyrinogen III.- Conversion of uroporphyrinogen to coproporphyrinogen by the enzyme uroporphyrinogen decarboxylase.- Conversion of coproporphynnogen lo protoporphyrinogen by the enzyme coproporphyrinogen oxidase.- Combination of iron with protoporphyrin.- Free protoporphyrin.- Regulation of Haem Biosynthesis.- Enzyme synthesis.- Changes in enzyme activity.- Regulation by substrate supply.- Metabolic and external factors.- Haem catabolism.- 4. Globin Synthesis.- Globin Biosynthesis.- General introduction.- Role of ribonucleic acids in globin synthesis.- Messenger RNA.- Isolation and identification of globin mRNA.- Methods used for the isolation of globin mRNA.- Detection of messenger RNA for globin.- Characteristics of globin mRNA.- Biosynthesis of globin mRNA.- Transfer RNA.- Ribosomes and globin synthesis.- Ribosome structure.- The role of polyribosomes.- The role of sub-units.- Membrane-bound ribosomes.- Function of the active ribosomal complex.- Initiation of the globin chain.- Initiation of globin synthesis by means of methionyl-tRNA.- Initiation factors of reticulocyte ribosomes.- Elongation of the globin chain.- Globin chain termination.- Regulation of Globin Synthesis.- Post-transcription control of globin synthesis.- Stability of globin mRNA.- Translation control.- Rate limiting step in the synthesis of the globin chain.- Synchronization of synthesis of different chains.- The role of haem in globin synthesis.- 5. Regulation of Haemoglobin Synthesis.- Coordination of Haem and Globin Syntheses.- Regulatory role of haem.- Mutual relations between haem and globin synthesis.- Haemoglobin Synthesis During Maturation.- 6. Differentiation of Erythroid Cells.- Erythroid Differentiation in Haematopoietic Tissue and the Initiation of Haemoglobin Synthesis.- Mechamun of erythropoietin action.- Erythroid Differentiation Without Erythropoietin.- 7. Anaemias Due to Disorders of Haemoglobinization.- Hypochromic Anaemias Due to Impaired Haem Synthesis.- Hypochromic anaemias caused by a reduced iron supply into erythroid tissue.- Iron deficiency anaemia.- Congenital atransferrinaemia.- Hypochromic anaemia as a result of reduced iron release from reticuloendothelial cells.- Copper defficiency.- Sideroblastic anaemias.- Hypochromic Anaemias Due to Impaired Globin Synthesis.- Thalassaemia.- ?-thalassaemia.- Haemoglobin Constant Spring and related mutants of the terminal portion of the chain.- ß- and ?ß-thalassaemia.- References.
1. Introduction.- 2. Substrate Supply for Haemoglobin Syntheses.- Iron Uptake.- Mechanism of iron supply to erythroid cells.- Factors influencing iron uptake by erythroid cells.- Iron and transferrin levels and transferrin saturation.- Metabolic state of crythroid cells.- The role of sulfhydryl groups in iron uptake.- Other factors which influence iron uptake.- Iron uptake from chelating agents.- Intracellular kinetics of iron.- Ferritin.- Other non-haem iron proteins and iron complexes.- Mitochondrial iron.- Inhibitors of haem synthesis as a tool in investigations of the intracellular kinetics of iron.- Regulation of iron supply for haemoglobin synthesis.- Effect of haem on iron uptake by reticulocytes.- Effort of inhibitors of haem and globin syntheses on iron uptake.- Mechanism of the effcct of haem on iron uptake.- Regulation of Uptake of Glycine and other Amino Acids.- 3. Haem Synthesis.- Biosynthesis of Haem.- General introduction.- ALA synthesis.- ALA synthetase.- Porphobilinogen (PBG) synthesis. ALA dehydrase enzyme.- Conversion of porphobilinogen (PBG) to uroporphyrinogen III.- Conversion of uroporphyrinogen to coproporphyrinogen by the enzyme uroporphyrinogen decarboxylase.- Conversion of coproporphynnogen lo protoporphyrinogen by the enzyme coproporphyrinogen oxidase.- Combination of iron with protoporphyrin.- Free protoporphyrin.- Regulation of Haem Biosynthesis.- Enzyme synthesis.- Changes in enzyme activity.- Regulation by substrate supply.- Metabolic and external factors.- Haem catabolism.- 4. Globin Synthesis.- Globin Biosynthesis.- General introduction.- Role of ribonucleic acids in globin synthesis.- Messenger RNA.- Isolation and identification of globin mRNA.- Methods used for the isolation of globin mRNA.- Detection of messenger RNA for globin.- Characteristics of globin mRNA.- Biosynthesis of globin mRNA.- Transfer RNA.- Ribosomes and globin synthesis.- Ribosome structure.- The role of polyribosomes.- The role of sub-units.- Membrane-bound ribosomes.- Function of the active ribosomal complex.- Initiation of the globin chain.- Initiation of globin synthesis by means of methionyl-tRNA.- Initiation factors of reticulocyte ribosomes.- Elongation of the globin chain.- Globin chain termination.- Regulation of Globin Synthesis.- Post-transcription control of globin synthesis.- Stability of globin mRNA.- Translation control.- Rate limiting step in the synthesis of the globin chain.- Synchronization of synthesis of different chains.- The role of haem in globin synthesis.- 5. Regulation of Haemoglobin Synthesis.- Coordination of Haem and Globin Syntheses.- Regulatory role of haem.- Mutual relations between haem and globin synthesis.- Haemoglobin Synthesis During Maturation.- 6. Differentiation of Erythroid Cells.- Erythroid Differentiation in Haematopoietic Tissue and the Initiation of Haemoglobin Synthesis.- Mechamun of erythropoietin action.- Erythroid Differentiation Without Erythropoietin.- 7. Anaemias Due to Disorders of Haemoglobinization.- Hypochromic Anaemias Due to Impaired Haem Synthesis.- Hypochromic anaemias caused by a reduced iron supply into erythroid tissue.- Iron deficiency anaemia.- Congenital atransferrinaemia.- Hypochromic anaemia as a result of reduced iron release from reticuloendothelial cells.- Copper defficiency.- Sideroblastic anaemias.- Hypochromic Anaemias Due to Impaired Globin Synthesis.- Thalassaemia.- ?-thalassaemia.- Haemoglobin Constant Spring and related mutants of the terminal portion of the chain.- ß- and ?ß-thalassaemia.- References.
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