B. Raaka, J. Lowenstein
May 10, 1979
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1
Influential Citations
22
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Journal
The Journal of biological chemistry
Abstract
DL-2-Rromooctanoate inhibits fatty acid oxidation in perfused rat liver and in mitochondria isolated from rat liver. Perfusion of livers for 12 min with 0.6 mu bromooctanoate causes complete and irreversible inhibition of ketogenesis from octanoate or oleate. Bromooctanoate also inhibits gluconeogenesis from lactate plus pyruvate but not from dihydroxyacetone. In isolated mitochondria, bromooctanoate irreversibly inhibits the oxidation of medium and long chain fatty acids and their L-carnitine esters. The extent of inhibition depends on the concentration of inhibitor and on the concentration of mitochondria. For example, 50% inhibition of palmitoyl L-carnitine oxidation is attained with about 2.5 nmol of bromooctanoate/mg of protein and 100% inhibition is attained with about 6 nmol of bromooctanoate/mg of protein. An energy-dependent activation of bromooctanoate occurs prior to the onset of inhibition. The conversion of bromooctanoate to its inhibitory form is not dependent on carnitine. Direct measurement of the content of coenzyme A and its derivatives in inhibited mitochondria indicates that the inhibitory effects of bromooctanoate are not caused by depletion of mitochondrial free CoA in the form of bromooctanoyl-CoA. Treatment of mitochondria with bromooctanoate does not prevent the subsequent formation of acyl-CoA from added fatty acid substrates. These and other results support the conclusion that an activated derivative of 2-bromooctanoic acid inhibits one or more of the enzymes of p-oxidation.