Effect of α-Bromo-palmitate on the Oxidation of Palmitic Acid by Rat Liver Cells

Rat liver cell suspensions oxidized [1-14C]palmitic acid and [1-14C]palmitoyl-l-carnitine efficiently to CO2. Oxidation of tracer amounts of palmitate was inhibited by α-bromo-palmitate (2 x 10-4 m). The oxidation of tracer amounts of palmitoyl-l-carnitine was not affected. α-Bromo-palmitoyl-dl-carnitine did not have any effect on the oxidation of either substrate. The inhibition of oxidation of tracer amounts of [1-14C]palmitate by the bromo-acid could be overcome by increasing the concentration of palmitic acid in the incubation medium. The oxidation of [1-14C]palmitic acid by liver mitochondria was also inhibited by α-bromo-palmitate but the inhibition could not be overcome by additional palmitate. α-Bromo-palmitoyl-dl-carnitine inhibited the oxidation of both palmitic acid and palmitoyl-l-carnitine by isolated mitochondria. The long chain acyl-CoA ligase activity of ultrasonically disrupted liver mitochondria was irreversibly inhibited by the α-bromo-palmitate but the long chain acyl-CoA-carnitine transferase was unaffected. Mitochondria isolated from liver cell which had been treated with α-bromo-palmitate were able to oxidize palmitic acid and had unimpaired long chain acyl-CoA ligase and acyl-CoA-carnitine transferase activities. The inhibition of fatty acid oxidation by cell suspensions in the presence of α-bromo-palmitic acid could be shown with palmitic, oleic, myristic, lauric, and decanoic acids but not with octanoic acid as substrates. From the results it is concluded that α-bromo-palmitic acid reversibly competes with a carrier mechanism of long chain fatty acid transport. It is suggested that long chain fatty acids do not cross the liver cell membrane by diffusion but probably by a mechanism involving fatty acid receptors on and across the membrane.