On the origin of bile pigment in normal man.

It has usually been assumed that bile pigment in the mammal is derived exclusively, or very nearly so, from the hemoglobin of mature, circulating red blood cells. Studies in the dog have revealed a close correspondence between the measurements of bile pigment excretion and the calculated degradation of hemoglobin of circulating red cells (3). A review of other studies in man, however, reveals less consistent results (4). The variations in results may be due merely to technical difficulties in the measurement of bile pigment or to errors in the assumptions that the hemoglobin of circulating erythrocytes is quantitatively converted to, and is the sole source of, bile pigment. In any case, conclusive proof has not been adduced for these assumptions. Another view, proposed by Whipple (5), was that bile pigment is derived to a significant extent from sources other than the hemoglobin of circulating erythrocytes. Conclusive experimental evidence for the existence and identity of other sources has, however, not been available. The studies described in this report offer evidence pertinent to the problem of the biologic origin of bile pigment. Previous studies have shown that glycine is specifically utilized in the biosynthesis of protoporphyrin (6) and that the administration of N16-labeled glycine provides a method for the determination of the average life span and pattern of destruction of the human erythrocyte in normal and pathologic states (7, 8). It was found that in normal man the average life span of the erythrocyte is approximately 120 days. It appears that very few of the mature, circulating erythrocytes are destroyed before the 40th day. Accordingly, if bile pigment is derived solely from the hemoglobin of mature, circulating erythrocytes, no significant concentration of N’s should be found in the bile pigment during the first 6 weeks after the administration of N15-labeled glycine. With the onset of destruction of red cells contain-