Reduced synthesis of hepatic microsomal cytochroma P450 in the bile duct ligated rat

Cholestasis produced by bile duct ligation was associated with a 50% reduction in hepatic microsomal cytochrome P₄₅₀ content. Tentative identification of cytochrome P₄₅₀ in washed microsomal fractions was achieved on SDS-urea polyacrylamide gels by its physical properties, half-life and response to pharmacologic agents. The relative synthesis rate of P₄₅₀ apoprotein, determined by a double isotope method, was significantly reduced 3 days after bile duct ligation. P₄₅₀ apoprotein degradation was markedly reduced, with the half-life increasing from 24 to 50 hours. These data indicate that a reduced rate of synthesis, rather than increased degradation, is responsible for reduction of P₄₅₀ in cholestasis.