PMID: 7288627Nov 1, 1981Paper

Role of reducing equivalents from fatty acid oxidation in mixed-function oxidation: studies with 2-bromooctanoate in the perfused rat liver

The Journal of Pharmacology and Experimental Therapeutics
M DanisR G Thurman


Mixed-function oxidation of p-nitroanisole in isolated perfused livers from fasted rats was studied in the presence and absence of 2-bromooctanoate, an inhibitor of the beta-oxidation of acyl CoA compounds. These experiments were designed to test the hypothesis that reducing equivalents from fatty acid oxidation may play a role in drug metabolism in the fasted state. Complete inhibition of ketogenesis, as indicated by beta-hydroxybutyrate and acetoacetate production, was achieved with the addition of 0.6 mM 2-bromooctanoate to the perfusate. This concentration of 2-bromooctanoate had no effect on p-nitroanisole O-demethylation measured in isolated microsomes but diminished maximal rates of p-nitroanisole O-demethylation by 78% in perfused livers of fasted, phenobarbital-treated rats. No inhibition of p-nitroanisole O-demethylation was seen in perfused livers from fed rats. Intracellular concentrations of ATP, NADH, glutamate, alpha-ketoglutarate and isocitrate decreased significantly in the presence of 2-bromooctanoate; oxygen uptake also decreased by about 50%. These data indicate that by inhibiting endogenous acyl CoA oxidation, 2-bromooctanoate diminishes beta-oxidation of fatty acids, thereby decreasing the supply of NADH f...Continue Reading

Related Concepts

2-bromooctanoate, (+-)-isomer
Adenine Nucleotides
Octanoic Acids
Saturated Fat
Mixed Function Oxygenases
Microsomes, Liver

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