MEASUREMENT OF SYNTHESIS RATES OF LIVER-PRODUCED PLASMA PROTEINS

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Abstract
[6-Cl4]Arginine was injected into rabbits and humans and guanidine carbon of plasma proteins was liberated enzymically as CO2. Specific activities of this carbon in gamma-globulins were many times higher than in liver-produced proteins, and marked reutilization of the injected C14 occurred. By "washing" C14-labelled albumins and C14-labelled fibrinogens with unlabelled gamma-globulins the accuracy of the measured specific activities of the guanidine carbon was improved. These were used in conjunction with the radioactivities of total [Cl4]urea to calculate rates of synthesis of albumin and fibrinogen in the rabbit. Values were somewhat lower than catabolic rates measured over a longer interval with I131-labelled albumin and I125-labelled fibrinogen. No significant advantage was apparent in making the synthesis measurement over an interval longer than 4 hours with albumin and 6 hours with fibrinogen. When [C14] carbonate was given as a single injection specific activities of the guanidine carbon of gamma-globulins were about one-half of those of liver-produced proteins, and reutilization was negligible. In adult humans a maximum of 0.02% of the injected radioactivity was incorporated into the guanidine carbons of plasma proteins. Fractional synthesis rates were calculated by using a formula independent of the arginine content of plasma proteins and their concentrations in the plasma. Close agreement was obtained between the catabolic rate (in experiments with I131-labelling) and the synthesis rate (in experiments with Cl4-labelling) of albumin in the rabbit, and evidence was obtained favoring a close association of urea synthesis and synthesis of guanidine carbons of albumin and fibrinogen in normal humans. A procedure is described for the use of 100-200 [mu]C of [C14]carbonate for measuring fractional synthesis rates of albumin and fibrinogen in humans, and results of its use are illustrated. Although the dose required for the same degree of labelling of protein is much higher than with [6-Cl4]arginine, the radiation hazard is less with [Cl4] carbonate, which also has other advantages.