Lack of control of liver gluconeogenesis in cholestatic rats with reduced portal blood flow

Authors

  • José Eduardo de Salles Roselino,

    Corresponding author
    1. Department of Biochemistry, University of Säo Paulo, 14049 Ribeiräo Preto SP, Brazil
    • Departamento de Bioquïmica, Faculdade de Medicina de Ribeirão Preto, USP, 14049 Ribeirão Preto, SP, Brasil
    Search for more papers by this author
  • Orlando de Castro-e-silva Jr.,

    1. Department of Surgery, School of Medicine of Ribeiräo Preto SP, University of Säo Paulo, 14049 Ribeiräo Preto SP, Brazil
    Search for more papers by this author
  • Reginaldo Ceneviva

    1. Department of Biochemistry, University of Säo Paulo, 14049 Ribeiräo Preto SP, Brazil
    Search for more papers by this author

Abstract

Previous studies indicated a role for ischemia in the metabolic changes induced by cholestasis. Liver pyruvate kinase is a key enzyme for the concurrent control of glycolysis and gluconeogenesis. In this experiment the control of pyruvate kinase activity was investigated in cholestatic rats. Pyruvate kinase kinetics changed from a sigmoidal type in sham-operated rats to a hyperbolic type in obstructed rats. The change in the enzymatic kinetics paralleled the reduction in the portal blood flow, which reached 50% of the control value 7 days after obstruction. Dibutyryl cyclic AMP (5 μmol/kg body wt) plus theophylline 0.1 mmol/L failed to inactivate the enzyme when injected into the portal veins of rats whose livers were obstructed 7 days before. Both the kinetics changes and the lack of phosphorylation control are compatible with ischemia. (HEPATOLOGY 1992;16:1055–1060.)

Ancillary