The Biosynthesis of Rat Serum Albumin: V. EFFECT OF PROTEIN DEPLETION AND REFEEDING ON ALBUMIN AND TRANSFERRIN SYNTHESIS

Abstract

Abstract The effects of protein depletion and repletion on the rate of albumin synthesis and on the levels of albumin in hepatic subcellular particles were measured in intact rats. A second serum protein of hepatic origin, transferrin, was measured simultaneously for comparison. A method capable of assaying albumin synthesis within a 16-min interval was developed in order to permit detection of rapid changes in rates of synthesis; in this procedure the total 14C-albumin content of intrahepatic albumin was divided by the integrated specific radioactivity of intrahepatic free 14C-l-leucine from the time of injection to the time of measurement. This method gave good agreement with measurements based on the circulating 14C-albumin at 2 hours after injection of the tracer. A 10-day period of protein depletion caused a 60 to 70% fall in rate of both albumin and transferrin synthesis, and a 40% fall in the quantities of these proteins bound in hepatic microsomes. Upon refeeding a complete mixture of amino acids by gavage, the level of microsomal albumin increased detectably within 15 min, and the rates of albumin and transferrin synthesis rose 50% within 30 min. This response was not inhibited by actinomycin D. These observations demonstrate the close control of albumin and transferrin synthesis by the amino acid supply in vivo. The amount of albumin in the intracellular albumin pool was observed to reach its normal level even before the circulating albumin level was restored, signifying that hypoalbuminemia can elicit increased synthesis without maintaining a decrease in the intracellular pool.