Inhibition of mixed-function oxidation in perfused rat liver by fluoroacetate treatment.
The effect of fluoroacetate, an inhibitor of the citric acid cycle, on the mixed-function oxidation of p-nitroanisole in isolated perfused livers from fed rats was studied. The citric acid cycle was inhibited by injection of 5 mg/kg sodium fluoroacetate into rats 3 hr prior to liver perfusion experiments. Inhibition of the citric acid cycle was marked by accumulation of citrate (5-fold) and decreases in rates of glycolysis and glycogenolysis by 50-90%. Fluoroacetate treatment inhibited mixed function oxidation in the perfused liver by about 50% without affecting p-nitroanisole O-demethylation by isolated microsomes. Fluorocitrate, at concentrations up to 50 microM, did not inhibit microsomal p-nitroanisole O-demethylation in vitro. These data support the hypothesis that mixed-function oxidation in intact hepatocytes is dependent upon reducing equivalents generated via the citric acid cycle.
D000818:Animals; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D005260:Female; D005463:Fluoroacetates / Q000494:pharmacology*; D005947:Glucose / Q000096:biosynthesis; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009575:Nitroanisole O-Demethylase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011773:Pyruvates / Q000096:biosynthesis; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D002951:Citrates; D005463:Fluoroacetates; D007773:Lactates; D011773:Pyruvates; D019343:Citric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; C014815:fluoroacetic acid; D006899:Mixed Function Oxygenases; D009575:Nitroanisole O-Demethylase; D005947:Glucose