Hemoglobin and Red Cell Structure and Function : Proceedings of the Second International Conference on Red Cell Metabolism and Function Held at the University of Michigan Ann Arbor, April 27–29, 1972

Hemoglobin and the red cell have continued to set a dizzying pace as the objects of research in the two and one-half year interval since the First International Conference on Red Cell Metabolism and Function. Most exciting perhaps, is a beginning molecular attack on sickle cell disease. The story of the inter­ action of red cell metabolism and oxygen transport has continued to unfold, and we can now infer that patients with hypoxia usually utilize red cell metabolic adjustments to improve oxygenation. This puts the red cell squarely in the center of medical practice, since much of medicine-heart, pulmonary, and blood disease- deals with inadequate oxygenation. On April 27th through the 29th, 1972, crystallographers, chemists, biochemists, physiologists, geneticists, and physi­ cians from many medical disciplines met in the Towsley Center for Continuing Medical Education at the University of Michigan, Ann Arbor to present new data, to review recent developments, and to try to piece together additional features of the red cell puzzle. The meeting was dedicated to Dr. Francis John Worsley Roughton, Professor Emeritus of Colloid Science, University of Cambridge, England, in recognition of his numerous excellent contributions to the understanding of hemoglobin and red cell function. The program got off to a good start with a paper from M. F. Perutz, Nobel Laureate, on the structure of hemoglobin. Dr. Front Matter....Pages i-xxxii Front Matter....Pages 1-1 Structure of Haemoglobin M Milwaukee, A Mutant Form Exhibiting Interaction Between Ferrous and Ferric Subunits....Pages 3-18 The Interaction Between Hemoglobin and Its “Oxygen-Linked” Ligands....Pages 19-40 The Interaction of Sickle Hemoglobin with DPG, CO 2 and with Other Hemoglobins: Formation of Asymmetrical Hybrids....Pages 41-53 Enhancement of the Acid and Alkaline Bohr Effects of Hemoglobin by Organic Phosphates....Pages 55-63 Functional Non-Equivalence of α and β Hemes in Human Hemoglobins....Pages 65-76 Front Matter....Pages 77-77 Hemoglobin Casper G8 β106 Leu→ Pro: Further Evidence that Hemoglobin Mutations are Not Random....Pages 79-98 Potential Effects of Hemoglobin Concentration on Red Cell Metabolism Together with Observations on Red Cell Metabolic Differences Between Men and Women....Pages 99-119 Catalase Activity and Red Cell Metabolism....Pages 121-131 Red Cell Hexosemonophosphate Shunt Deficiency in Uremia....Pages 133-143 Effect of Inorganic Phosphate on Red Cell Metabolism: In Vitro and In Vivo Studies....Pages 145-154 Studies of the Metabolic Basis of the ATP-DPG Differences in Genetically Selected High and Low ATP-DPG Rat Strains....Pages 155-164 Front Matter....Pages 165-165 Introductory Remarks at the Beginning of Session III....Pages 167-168 Functional Aspects of the Three-Dimensional Structure of the Active Site of Carbonic Anhydrase....Pages 169-187 The Effect of Temperature on the Catalytic Activity of Bovine Carbonic Anhydrase....Pages 189-199 Carbonic Anhydrase, Red Cell Membranes, and CO 2 Transport....Pages 201-208 Effect of Chlorthalidone Binding on the Electrophoretic Properties of Human Red Cell Carbonic Anhydrase Isozymes....Pages 209-213 The Role of Carbonic Anhydrase in the Control of Intracellular pH....Pages 215-224 The Contribution of Carbamate in Human Adult and Foetal Blood to the CO 2 Exchange During the Respiratory Cycle....Pages 225-236 Front Matter....Pages 237-237 Introductory Remarks at the Beginning of Session IV....Pages 239-241 Thermal (Or Endothermic) Aggregation of Sickle Cell Hemoglobin (Hb S) During Sickling....Pages 243-251 Front Matter....Pages 237-237 Chemical and Biological Aspects of the Inhibition of Red Blood Cell Sickling by Cyanate....Pages 253-260 Preliminary Clinical Trials with Cyanate....Pages 261-278 Carbamyl Phosphate Modification of Hemoglobin S Structure Resulting in Altered Sickling....Pages 279-296 Oxygen Affinity Independent Action of Cyanate and 2,3 DPG on Sickling....Pages 297-302 Evaluation of Oral Urea in the Management of Sickle Cell Anemia....Pages 303-323 The Sickling Phenomenon of Deer Erythrocytes....Pages 325-336 Further Studies on the Antenatal Detection of Sickle Cell Anemia and other Hemoglobinopathies....Pages 337-346 Front Matter....Pages 347-347 Adjustments of the Oxygen Transport System During Residence at High Altitude....Pages 349-360 Red Cell Metabolism and Oxygen Affinity of Healthy Individuals During Exposure to High Altitude....Pages 361-375 Enzymatic Mechanisms of Red Cell Adaptation to Anemia....Pages 377-396 Red Cell Metabolic Changes in Acute and Chronic Exposure to High Altitude....Pages 397-413 Effects of Cyanate in Rabbits....Pages 415-430 Front Matter....Pages 431-431 Studies on the Ability of Stored Blood to Transport Oxygen In Vivo....Pages 433-447 The Two Bohr Effects: Physiological Consequences of Ligand Interaction with Hemoglobin....Pages 449-455 Rejuvenation and Freezing of Outdated Human Red Cells....Pages 457-477 Effects of Adenine on Stored Human Red Cells....Pages 479-494 Hemoglobin Function During Blood Storage XV: Effects of Metabolic Additives Inosine and Methylene Blue on p50 and 2,3-DPG....Pages 495-509 The Effect of Massive Transfusion of Stored Blood on Oxygen Transport — A Preliminary Report....Pages 511-516 Back Matter....Pages 517-526 Hemoglobin and the red cell have continued to set a dizzying pace as the objects of research in the two and one-half year interval since the First International Conference on Red Cell Metabolism and Function. Most exciting perhaps, is a beginning molecular attack on sickle cell disease. The story of the interaction of red cell metabolism and oxygen transport has continued to unfold, and we can now infer that patients with hypoxia usually utilize red cell metabolic adjustments to improve oxygenation. This puts the red cell squarely in the center of medical practice, since much of medicine-heart, pulmonary, and blood diseases - deals with inadequate oxygenation. On April 27th through the 29th, 1972, crystallographers, chemists, biochemists, physiologists, geneticists, and physicians from many medical disciplines met in the Towsley Center for Continuing Medical Education at the University of Michigan, Ann Arbor to present new data, to review recent developments, and to try to piece together additional features of the red cell puzzle. The meeting was dedicated to Dr. Francis John Worsley Roughton, Professor Emeritus of Colloid Science, University of Cambridge, England, in recognition of his numerous excellent contributions to the understanding of hemoglobin and red cell function. The program got off to a good start with a paper from M. F. Perutz, Nobel Laureate, on the structure of hemoglobin. Dr. Perutz also key-noted the Conference with a special lecture on heme-heme interaction. A number of fascinating papers were presented on various aspects of hemoglobin, its structure, its interaction with ligands such as oxygen, and its properties under varying conditions. Red cell metabolism was considered, in depth, from many viewpoints, including defects in uremia, interactions with serum phosphorous, male-female differences, the role of catalase, genetic selection for quantitative variation, and mechanisms of glycolytic response to altitude stress and to anemia. As with the first conference, a session was devoted to the continuing assessment of the importance of decline in red cell oxygen transport functional capacity during blood bank storage. A session was also devoted to consideration of carbonic anhydrase and carbon dioxide transport, and the interaction of this area with oxygen transport. A high point of the conference was the session on sickle cell structure and function. Excellent papers were presented on cyanate, including results of some early clinical trials which look promising. A trial with oral urea in sickle cell disease indicating possible usefulness of this approach was presented. The antisickling properties of carbamyl phosphate were also discussed. The present status of prenatal diagnosis of sickle cell disease, and the sickling phenomenon of deer erythrocytes, were other interesting topics. The discussions in the general area of sickle cell disease and the mechanisms by which antisickling agents act were quite interesting because of the diversity and expertise represented in the audience. This volume contains the Proceedings of this second conference. It includes the formal papers and much of the informal discussion after the papers. It represents a compilation of the present state of the art, and the status of current thinking, in the various areas discussed above.