Metabolic fate of fatty acids in the carnitine cycle of brown adipose tissue mitochondria

Abstract

Freshly isolated mitochondria from brown adipose tissue are uncoupled with respect to oxidative phosphorylation. When these mitochondria oxidize[U-minus 14-C] palmitic acid in the presence of malate the label is found in three major fractions. Polar lipids, rich in acyl carnitines, remain in the mitochondrial pellet. A large fraction, rich in tricarboxylic acid cycle intermediates, is exported to the suspending medium, as is a third, smaller fraction containing ketone bodies and beta-hydroxy-beta-methylglutaric acid. Prevention of oxygen uptake by addition of rotenone or antimycin prevents accumulation of cycle intermediates, increases formation of acyl carnitiness and increases beta-hydroxybutyrate relative to acetoacetate. Rotenone and antimycin do not prevent formation of labeled phosphatidylcholine. Partial suppression of oxygen uptake by benzene-1,2,3-tricarboxylic acid, amytal or malonate leads to results between these extremes. Addition of lysophosphatidylcholine had minimal effects on export of cycle intermediates, but increased formation of ketone bodies and particularly of acyl carnitines. The significance of lysophosphatidylcholine as an endogenous modifier of mitochondrial metabolism is discussed.