Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type

The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte.