Hexa- and pentapeptide extension of proalbumin: feedback inhibition of albumin synthesis by its propeptide in isolated hepatocytes and in the cell-free system.

Addition of the chemically synthesized proalbumin hexapeptide in a concentration of 110 micro M to the medium of isolated rat hepatocytes decreased net albumin synthesis by 12%. The synthesis of other secretory proteins was not altered. A weaker inhibitory effect on albumin synthesis was found for a tetrapeptide, a possible degradation product of the proalbumin hexapeptide. For the uptake of the hexa- and tetrapeptide into the cells, bovine serum albumin is required. In a reticulocyte and in a wheat germ cell-free system a propeptide concentration of 600 micro M inhibited albumin synthesis by 50%, whereas total protein synthesis was inhibited by 19% only, and the synthesis of alpha 1-antitrypsin was not inhibited. These results suggest that the synthesis of preproalbumin is regulated by a feedback mechanism with its propeptide as inhibitor.