The use of radioactive lysine in studies of protein metabolism; synthesis and utilization of plasma proteins.

Racemic lysine labeled with C(14) in the epsilon carbon position was fed to dogs. The distribution of C(14) in blood and tissue fractions is recorded. In normal dogs sacrificed at 24 hours, approximately one-third of the C(14) was found in the urine, one-third in expired air, and one-third in the body, mostly in protein, predomantly as lysine residues. The rate of C(14) excretion as CO(2), hour by hour, paralleled closely the amount of non-protein C(14) in the blood plasma. The liver, kidney, pancreas, and spleen all have high values for C(14) in 24 hour and 17 day experiments. The gastrointestinal tract is significantly high in the 24 hour experiments. Plasma protein from animals previously fed C(14) containing lysine and thus in turn labeled, was transfused into other dogs and the rate of disappearance of albumin and globulin fractions from the circulation of the recipient dog followed. The results lead to the conclusion that as a whole, plasma proteins are utilized and replaced at a rate of at least 10 per cent per 24 hours. This minimum rate is substantially faster than turnover rates commonly accepted and emphasizes the rôle played by the plasma proteins in the protein economy of the body. The exact rate determination is made uncertain by the lack of knowledge of the magnitude of the amount of protein in solution in extracellular and lymph spaces and its rate of equilibrium with circulating plasma proteins. Evidence from these transfusion studies indicates that plasma globulin is metabolized at a significantly faster rate than plasma albumin. This is confirmed by the observation that following the feeding of labeled lysine to dogs, C(14) is first incorporated in globulin in high concentration but that later it also disappears more rapidly from the globulin fraction. These data suggest that the period of bone marrow maturation of the red cell during which time its related hemoglobin is synthesized does not exceed 3 to 5 days.