Experimental study on the mechanism of hyperphosphatasaemia in bile flow obstruction

Extrahepatic bile flow obstruction is followed by a several-fold increase in alkaline phosphatase activity in the liver. This activity passes into the blood. The increase in the activity of the enzyme in the liver can be prevented by inhibitors of RNA and protein synthesis. Inducible alkaline phosphatase was purified from rat liver and 1,000-fold purification was achieved. The incorporation of labbelled precursors (14C amino acids and 14C glucosamine) into the liver alkaline phosphatase was evaluated. No significant difference were found between specific alkaline phosphatase activities and specific radioactivities in the control rats and rats with 7.30 h after bile duct obstruction. The incorporation of 14C-amino acids into the total liver proteins was 20% lower in rats with cholestasis than in the control group. The results are evidence that the liver is the source of elevated alkaline phosphatase activity in serum in cholestasis, and that the production of alkaline phosphatase in the liver is prevented by inhibitors of RNA a protein synthesis. However, the enzyme might be synthesized before the 14C-labelled precursors were applied.