Induction of rat liver alkaline phosphatase: the mechanism of the serum elevation in bile duct obstruction.
Bile duct ligation in the rat leads to a rapid increase in hepatic and serum alkaline phosphatase activity. Within 12 hr after bile duct ligation, hepatic alkaline phosphatase has increased 7-fold and serum alkaline phosphatase activity 2(1/2)-fold. The elevation in the serum activity is completely due to an increase in an isozyme that appears to originate in the liver. This serum isozyme and liver phosphatase, both partially purified by DEAE-cellulose column chromatography, have identical Michaelis constants, pH optima, and rates of heat denaturation. These isozymes migrate identically when subjected to electrophoresis on polyacrylamide gel, and their migration rates are equally slowed after neuraminidase digestion. The data suggest that the rise in hepatic alkaline phosphatase activity is dependent on de novo protein synthesis. Cycloheximide, in a dose that inhibited incorporation of leucine-(14)C into protein by 68%, inhibited the rise in liver phosphatase by 98% and that in serum by 80%. The rise in liver phosphatase activity could not be accounted for by simple retention of alkaline phosphatase that would normally appear in bile. The rise in liver activity after bile duct ligation was 240 times greater than the amount of phosphatase that normally appears in bile over a similar period of time. Cycloheximide had no effect on the bile duct ligation-induced changes in the serum and liver glutamic pyruvic transaminase.
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000201:enzymology; D001652:Bile Ducts / Q000601:surgery; D002247:Carbon Isotopes; D002848:Chromatography, DEAE-Cellulose; D003513:Cycloheximide / Q000494:pharmacology; D004586:Electrophoresis; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008107:Liver Diseases / Q000201:enzymology; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D013997:Time Factors
D002247:Carbon Isotopes; D007527:Isoenzymes; D003513:Cycloheximide; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007930:Leucine