| Abstrakt: |
Previous reports have shown that tube feeding intact rats or mice an amino acid mixture lacking the single amino acids l-tryptophan or l-threonine results in gross alterations in hepatic polyribosome profile and in changes in hepatic and plasma protein synthesis estimated in terms of incorporation of 14C amino acids; in brief, because the effects of tryptophan and threonine removal were described to be qualitatively and quantitatively different, the experiments in this study were undertaken.The effects on liver and plasma protein synthesis of total exclusion of either l-tryptophan or l-threonine from an otherwise nutritionally complete amino acid mixture were studied in the isolated perfused rat liver. Livers of normal adult male Sprague-Dawley rats were isolated and perfused with a heparinized suspension of rabbit red cells in Krebs-Ringer bicarbonate buffer containing 3% bovine serum albumin. This heterologous perfusion medium permitted the serological measurement of net increases in the biosynthesis of five specific plasma proteins: albumin, fibrinogen, α1-acid glycoprotein, α2-(acute phase) globulin, and haptoglobin during the 12 hr of perfusion.Livers from fed or 18-hr fasted liver donors were perfused under conditions favoring maximal net synthesis of specific plasma protiens, i.e., with continuous infusion of insulin plus hydrocortisone as well as glucose and the amino acid mixture; removal of tryptophan only elicited a minimal decrease in albumin synthesis by livers from 18-hr fasted donors and supported both optimal synthesis and induction of increased synthesis of fibrinogen, α1-acid glycoprotein, and haptoglobin. Synthesis of α2-(acute phase) globulin was impaired in three of six perfusions with the tryptophan-deficient mixture in livers from fed donors.Removal of threonine only resulted in unaltered net albumin, fibrinogen and haptoglobin synthesis by livers from both fed and 18-hr fasted liver donors, but enhanced the net synthesis of α1-acid glycoprotein by livers from fed rats.Removal of either amino acid did not impair the incorporation of l-lysine-1-14C into the gross hepatic proteins from livers of both fed and fasted donors.Both removal of tryptophan and threonine resulted in overall negative nitrogen balance for the perfusion system with livers from fed donors; with livers from fasted donors the negative balance effect of tryptophan removal is greatly lessened, whereas threonine removal was altogether without effect. It appears that the isolated perfused liver is capable of catabolizing enough protein from hepatic cells, perfusate red cells, or albumin to supply the tryptophan and threonine needed for the substantial net synthesis of the five plasma proteins observed. |
