Lack of control of liver gluconeogenesis in cholestatic rats with reduced portal blood flow.
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 mumol/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.
Roselino
J E
JE
Department of Biochemistry, School of Medicine of Ribeirão Preto SP, University of São Paulo, Brazil.
De Castro-e-Silva Júnior
O
O
Ceneviva
R
R
D000818:Animals; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology*; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D005635:Fructosediphosphates / Q000494:pharmacology; D005943:Gluconeogenesis; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011168:Portal System / Q000503:physiopathology*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D005635:Fructosediphosphates; D000242:Cyclic AMP; D011770:Pyruvate Kinase; C029063:fructose-1,6-diphosphate