Regulation of Net Biosynthesis of Serum Albumin and Acute Phase Plasma Proteins

Abstract

Abstract Livers isolated from normal, male, fed rats were perfused for 12 hours with bovine or rabbit red blood cells suspended in Krebs-Ringer-bicarbonate solution containing bovine serum albumin (3.0 g/100 ml) with l-lysine-1-14C and 500 mg of glucose continuously infused. Net synthesis of five specific plasma proteins was estimated by serological measurements of changes in their concentration in perfusate. The influence of insulin, cortisol, and growth hormone, and of a nutritionally complete mixture of amino acids on net synthesis of plasma proteins was evaluated. Control perfusions (no hormones or amino acids added) resulted in relatively linear net synthesis of the specific plasma proteins throughout the experiments. In experiments with full supplementation (insulin, cortisol, growth hormone, and the amino acid mixture) fibrinogen and haptoglobin synthesis increased 3-fold between 2 and 6 hours, α1-acid glycoprotein synthesis increased 3.5-fold between 4 and 8 hours, and α2 (acute phase)-globulin synthesis increased 11-fold between 8 and 10 hours. Increases in the latter four proteins were critically dependent upon the presence of cortisol and represented the first demonstration in vitro of hormone effects on net plasma protein synthesis. These effects may be important for understanding the increased blood levels of certain plasma α and β globulins that occur in vivo in mammals after many forms of injury and may serve as a useful model for furthering our understanding of the influence of hormones and amino acids on protein synthesis. Maximum net plasma protein synthesis occurred in perfusions with positive nitrogen balance (more net amino acid nitrogen loss from perfusate than urea nitrogen gain). Under the conditions employed the combination of amino acids and insulin was the minimal partial supplementation required for positive nitrogen balance. Additional data are presented on effects of amino acids and hormones on incorporation of l-lysine-1-14C into total plasma proteins and hepatic proteins, oxidation of l-lysine-1-14C to 14CO2, production of bile, utilization of glucose, net urea synthesis, net changes in amino acid nitrogen, and on nitrogen balance as defined for the liver perfusion system.