Influence of malonyl-CoA and palmitate concentration on rate of palmitate oxidation in rat muscle.
5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) is taken up by perfused skeletal muscle and phosphorylated to form 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuraosyl-5'-monopho sph ate (analog of 5'-AMP) with consequent activation of AMP-activated protein kinase, phosphorylation of acetyl-CoA carboxylase, decrease in malonyl-CoA, and increase in fatty acid oxidation. This study was designed to determine the effect of increasing levels of palmitate on the rate of fatty acid oxidation. Malonyl-CoA concentration was manipulated with AICAR at different palmitate concentrations. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red cells, 200 microU/ml insulin, 10 mM glucose, and different concentrations of palmitate (0. 1-1.0 mM) without or with AICAR (2.0 mM). Perfusion with medium containing AICAR was found to activate AMP-activated protein kinase in skeletal muscle, inactivate acetyl-CoA carboxylase, and decrease malonyl-CoA at all concentrations of palmitate. The rate of palmitate oxidation increased as a function of palmitate concentration in both the presence and absence of AICAR but was always higher in the presence of AICAR. These results provide additional evidence that malonyl-CoA is an important regulator of the rate of fatty acid oxidation at palmitate concentrations in the physiological range.
Merrill
G F
GF
Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, New Jersey 08854, USA.
Kurth
E J
EJ
Rasmussen
B B
BB
Winder
W W
WW
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D010168:Palmitates / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012265:Ribonucleotides / Q000494:pharmacology
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D010168:Palmitates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008316:Malonyl Coenzyme A; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide