malonyl-coenzyme-a and acadesine

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 microU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.

Topics: Acetyl-CoA Carboxylase; Adenine Nucleotides; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Cattle; Enzyme Activation; Erythrocytes; Glucose; Hindlimb; Insulin; Kinetics; Male; Malonyl Coenzyme A; Multienzyme Complexes; Muscle, Skeletal; Palmitic Acid; Phosphorylation; Protein Kinases; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Ribonucleosides; Ribonucleotides; Serum Albumin, Bovine