Proteins in multiple myeloma. III. Origin of Bence-Jones protein

1955 Journal of Biological Chemistry  
Multiple myeloma is of biochemical interest because the profuse synthesis and the diverse nature of t.he proteins elaborated by different patients represent one of the most profound alterations in protein metabolism yet encountered. This disease of unknown etiology is generally classified with the tumors. It is believed to affect the plasma cells that are implicated in globulin synthesis and antibody production. Multiple myeloma results in any one or more of three aberrations in protein
more » ... sm: (1) the production of anomalous serum globulins, (2) the excretion of characteristic urinary (Bence-Jones) proteins, and (3) the deposition of protein in the tissues (paramyloidosis) (1). The proteinuria occurs more commonly in the absence of hyperglobulinemia than in its presence. The origin of the Bence-Jones protein is uncertain but has been ascribed to renal cleavage of myeloma globulins (2, 3) or degradation of tissue proteins. Physicochemical characterization (4, 5) and end-group analysis (6) have established that there are different types of myeloma globulins and of Bence-Jones proteins, but have failed to elucidate their relationship to each other and to normal serum proteins. Investigation with isotopic tracers of the rate of synthesis and possible precursor relationships of myeloma globulins and Bence-Jones proteins has therefore been undertaken (7, 8) . For the present study labeled glycine, NH&HzC?~OOH, was given to a patient whose serum contained 5 gm. per cent of an abnormal "p"-globulin, and who excreted 1 to 2 gm. of Bence-Jones protein daily. The abnormal globulin and the urinary protein were isolated from samples taken over a period of 50 days, and the purity of the fractions was ascertained by electrophoretic and ultracentrifugal analyses. The proteins were hydrolyzed, and glycine was separated chromatographically. The Cl3 content of the carboxyl carbon was estimated in the mass spectrometer. From the time course of the Cl3 decline, it is concluded that the rates of synthesis of the two pathological proteins are independent and that the urinary protein is not derived from any known serum or tissue protein. Although the half life of the myeloma globulin was possibly longer than that of normal serum
pmid:13233238 fatcat:xoza6ali75e7pawgfvdk5iyonq