THE INABILITY OF HUMAN OR BEEF GLOBIN TO SUPPORT NORMAL HEMATOPOIESIS IN THE RAT WITHOUT ADDED ISOLEUCINE

Abstract

The fact that dried beef blood, added as the source of protein to an otherwise adequate synthetic diet, failed to support normal growth and hemoglobin regeneration in the rat has been demonstrated in earlier work in this laboratory (1, 2).The substitution of milk proteins for a part of the dried beef blood, on the other hand, permits good growth and the maintenance of normal hemoglobin format.ion,thus suggesting that the proteins of beef blood are of the "incomplete" type.Since whole blood contains a number of distinct proteins, it seemed necessary to investigate next the various isolated blood proteins for adequacy in supporting growth and hematopoiesis.The protein, globin, was selected first, since it is quantitatively the predominant prot,ein of whole blood.Preliminary results (3) indicated that neither purified human nor beef globin was adequate for supporting a normal rate of growth or hemoglobin formation in the rat.After the globin-containing diet had been fed for 4 to 6 weeks, a rapid decrease in body weight occurred, an anemia developed, and death invariably resulted.While this investigation was in progress, a report of the amino acid composition of beef hemoglobin appeared (4), showing that this protein contains a relatively small amount of isoleucine.Some time later two separate investigations (5, 6) demonstrated that hemoglobin or globin, fed as the source of protein in an adequate diet, failed to support growth in the rat, whereas the addition of isoleucine promptly resulted in a satisfactory increase in body weight.Preliminary results in this laboratory (3) confirmed this observation.The present investigation was designed to determine the effect of isoleucine on hematopoiesis in anemic rats fed a synthetic diet containing purified human or beef globin as the protein.EXPERIMENTAL 21 day-old male rats, weighing from 40 to 50 gm., of the Connecticut Agricultural Experiment Station strain were used.They were housed in