Oxidative metabolism of long-chain fatty acids in mitochondria from sheep and rat liver. Evidence that sheep conserve linoleate by limiting its oxidation.
Mitochondria isolated from the livers of sheep and rats were shown to oxidize palmitate, oleate and linoleate in a tightly coupled manner, by monitoring the oxygen consumption associated with the degradation of these acids in the presence of 2mM-L-malate. Rat liver mitochondria oxidized linoleate and oleate at a rate 1.2-1.8 times that of palmitate. Sheep liver mitochondria had a specific activity for the oxidation of palmitate that was 50-80% of that of rats and a specific activity for the oxidation of oleate and linoleate that was 30-40% that of rats. This would indicate that sheep conserved linoleate by limiting its oxidation. Carnitine acyltransferase I (CAT I) actively esterified palmitoyl-CoA and linoleate to carnitine in both rat and sheep liver mitochondria, and in both cases the rate for linoleate was faster than for palmitate. The CAT I reaction in both rat and sheep liver was inhibited by micromolar amounts of malonyl-CoA. With 90 microM-palmitoyl-CoA as substrate, CAT I was inhibited by 50% with 2.5 microM-malonyl-CoA in rats, and in sheep, 50% inhibition was found with all malonyl-CoA concentrations tested (1-5 microM). With 90 microM-linoleate as substrate for CAT I, a much larger difference in response to malonyl-CoA was seen, the rat enzyme being 50% inhibited at 22 microM-malonyl-CoA, whereas sheep liver CAT I was 91% and 98% inhibited at 1 microM- and 5 microM-malonyl-CoA respectively. We propose that malonyl-CoA may act as an important regulator of beta-oxidation in sheep, discriminating against the use of linoleate as an energy-yielding substrate.
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep
D005227:Fatty Acids; D008041:Linoleic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D019301:Oleic Acid; D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; D019787:Linoleic Acid; D002334:Carnitine O-Palmitoyltransferase