The formation of bile pigment in pernicious anemia.

Studies on the origin of bile pigment in normal man have revealed that a significant portion of bile pigment is derived from one or more sources other than the hemoglobin of mature, circulating erythrocytes (3). This finding suggested the possibility that the markedly increased quantities of bile pigment excreted in untreated pernicious anemia might also be derived in part from sources other than the hemoglobin of mature, circulating erythrocytes. Such a possibility is not in accord with the assumption, made by most investigators in the past, that the increased quantities of bile pigment which are excreted are the result solely of an abnormally increased rate of hemolysis (4). This assumption has been challenged by others (5, 6) who have held that the rate of turnover of hemoglobin and circulating erythrocytes which would be required to produce such large quantities of bile pigment was improbably high. Conclusive evidence in support of either position, however, was not available. The study described in this report was performed to provide information which might help to elucidate the relationship of hemoglobin metabolism to the formation of bile pigment in pernicious anemia. The administration of glycine labeled with N15 affords a method for the study of the life span and pattern of destruction of the human erythrocyte in normal and pathologic states (7, 8). This method was used to study heme synthesis and dynamics of the red blood cell in a patient with the characteristic symptoms of pernicious anemia. The curve of N15 concentration in the hemin of this subject has been described previously (8). At the start of the experiment the patient had received no antianemia therapy. Glycine labeled with N15 was fed for 2 days. After 15 days, when the isotope concentration in the hemin appeared to be approaching it,s maximum value, it was considered inadvisable to withhold treatment longer, and liver extract in large dosage was administered. Analysis of the data re-