title: Regulation of fatty acid oxidation in rat brain mitochondria: inhibition of high rates of palmitate oxidation by ADP.
abstract: Regulation of oxidation of [1-14C]palmitate in rat brain mitochondria has been investigated in purified mitochondria of nonsynaptic origin prepared by use of a Ficoll/sucrose density gradient. The mitochondrial preparation contained considerable Mg2+-ATPase activity, but was virtually free of contamination with nonmitochondrial fractions. Palmitate oxidation was inhibited by increasing the concentration of ATP in the assay system to near-physiological levels (2 mM), and the inhibition at 2 or 4 mM ATP was analyzed by comparing it with palmitate oxidation at near-maximal rates with low levels of ATP (0.5 or 1 mM). Inhibition was increased by the addition of ADP or by increasing the concentration of Mg2+ in the assay system, whereas inhibition was decreased by decreasing the concentration of mitochondrial protein or L-carnitine in the assay system. Increasing CoA concentration also had a deinhibitory effect. With 0.5 or 1 mM ATP, however, neither inhibition by added ADP nor protein concentration-dependent inhibition was observed, and the rate of oxidation was saturated with increasing concentrations of Mg2+, L-carnitine, or CoA. These results indicated that ADP was involved in the inhibition of high rates of palmitate oxidation in the presence of sufficient ATP and L-carnitine. The inhibitory effect of increasing the concentration of mitochondrial protein could be explained by the enhanced amounts of ADP present in the preparation; similarly, increased concentrations of Mg2+ would provide higher levels of ADP by stimulating the Mg2+-ATPase reaction. We discuss the possibility that the transport of ADP across the inner membrane of brain mitochondria is coupled to the inhibition of palmitate oxidation.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002331:Carnitine / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D003065:Coenzyme A / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005227:Fatty Acids; D010169:Palmitic Acids; D011506:Proteins; D019308:Palmitic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D008274:Magnesium; D002331:Carnitine; D003065:Coenzyme A; D002118:Calcium