Proteins in multiple myeloma. V. Synthesis and excretion of Bence-Jones protein.

Oral administration of amino acids labeled with N15 or with Cl3 to patients with multiple myeloma, followed by isolation of the abnormal serum and urinary proteins, has led previously to the conclusion that Bence-Jones protein is not derived by cleavage of circulating serum proteins nor by degradation of tissue proteins (1, 2). In point of fact, no evidence for any kind of precursor relationship between the two types of abnormal proteins was found. The data from these experiments also suggested that the Bence-Jones protein is formed rapidly de nov,o from free amino acids and is excreted rapidly. However, the stable isotopes proved unsuitable for the precise study of the rate of synthesis and excretion of Bence-Jones protein because they are too insensitive for intravenous administration at tracer levels and for measurement of the isotopic concentration of the unhydrolyzed protein. Thus, for the present work lysine, uniformly labeled with C14, was chosen to facilitate the rate study. The lysine was injected into a subject who copiously excreted Bence-Jones protein but lacked an abnormal serum globulin. The urine was collected by urethral catheter, and the specific activity of the purified protein specimens was determined. The activity was maximal at 10 hours and thereafter declined rapidly. This indicates that the urinary protein was synthesized from the free amino acids rather than from preformed tissue proteins and that Bence-Jones protein, once released into the circulation, is treated like other nitrogenous excretory products, despite its size.