The Heme-globin Linkage of Hemoglobin I. the Course of the Pancreatic Digestion of Oxyhemo- Globin and of Carboxyhemoglobin by William F. Ross

At four positions within the native globin molecule heme may combine to give a protein, capable of reversible combination with oxygen (1, 2) and identical with hemoglobin (3, 4). As many as thirty hemes may react with denatured globin, but the product cannot be reversibly oxygenated. Many other nitrogen-containing compounds combine with reduced hematin to form hemochromogens, but none of these combines with oxygen in this way. Particular interest is therefore attached to the nature of the union of heme to globin in native hemoglobin. Analogies between hemoglobin and simpler derivatives have given some information about this point. Among the methods used have been electrometric titration, and the study of the magnetic properties, and oxidation-reduction potentials of the iron atom. More direct have been efforts to keep intact the original heme-protein linkage during degradation of the protein, chemical and enzymic hydrolytic agents having been employed. Waelsch (5) treated hemoglobin with 2 per cent sodium hydroxide at 85”, and isolated from the reaction a product containing hematin, proline, and alanine. By alcoholysis of hemoglobin at 190”, Kiister and Koppenhofer (6), also, obtained a proline-hematin fraction. No further support for the association of heme with proline has been presented. Haurowitz degraded hemoglobin with the tryptic (7) and papain (8) enzymes, both giving a product, “hemin proteose,” rich in iron, with a molecular weight of “at