Evidence for the coupling of biosynthesis and secretion of serum albumin in the rat. The effect of colchicine on albumin production.

1. By using isotopic-dilution techniques it was found that colchicine causes a slight increase in the proalbumin content of liver, from 0.63+/-0.06 to 0.83+/-0.10mg/g of liver, but has no effect on albumin content (0.50+/-0.05mg/g of liver). All the proalbumin and 67% of the albumin is found in vesicles from which they are liberated by detergents. 2. Colchicine inhibits secretion of albumin, decreases the rate of conversion of proalbumin into albumin and decreases the rate of incorporation of l-[1-(14)C]leucine into proalbumin. 3. Balance studies in vivo show that all the (14)C appearing in serum albumin can be accounted for by the flow of (14)C through the proalbumin, in the presence or absence of colchicine. 4. When cycloheximide is given to the rats, 2min after [(14)C]leucine, further synthesis of protein stops. The label in proalbumin disappears and the proalbumin content of the liver falls, so as to account for the albumin appearing in the plasma. This occurs both in the presence and in the absence of colchicine. By contrast, there is little change in liver albumin. Studies with isolated perfused livers are in agreement with the above. Lumicolchicine has no effect on any of these systems at doses at which colchicine exerts its action. 5. These results suggest that biosynthesis and conversion of proalbumin into albumin, and secretion of serum albumin are controlled at each step.