Import of palmitoyl-CoA into the mitochondrial matrix Activated AMPK stimulates fatty-acid oxidation in muscle AMPK plays a central role in regulating fatty acid oxidation in muscle. In order for fatty acids taken up and converted to fatty acyl CoA’s by muscle cells to undergo beta-oxidation, they must be transported into the mitochondrial matrix by carnitine palmitoyl transferase (CPT). This transport process is negatively regulated by malonyl CoA, synthesized by ACC2 enzyme on the outer mitochondrial membrane. Phosphorylation and activation of AMPK as a result of signaling via leptin, adiponectin, and alpha-adrenergic receptors, however, enables this enzyme to phosphorylate and <b><i>in</b></i>activate ACC2, reducing the levels of malonyl CoA and thus facilitating CPT-mediated fatty acid transport (Kahn et al.,2005). <br>The mitochondrial CPT transport system consists of the malonyl-CoA sensitive carnitine palmitoyltransferase I (CPT-I) localized in the mitochondrial outer membrane, the carnitine:acylcarnitine translocase, an integral inner membrane protein, and carnitine palmitoyltransferase II localized on the matrix side of the inner membrane (Kerner and Hoppel, 2000).<br>In this module, the effect of activated AMPK on fatty acid beta oxidation as mediated by malonyl CoA in muscle cells is annotated. The mechanisms by which leptin and adrenergic receptors modulate AMPK activity will be annotated in the future. Authored: Gopinathrao, G, 2007-07-29 21:03:03 GENE ONTOLOGYGO:0046320 Pubmed10856709 Pubmed11797013 Pubmed16054041 Reactome Database ID Release 43200409 Reactome, http://www.reactome.org ReactomeREACT_11163 Reviewed: D'Eustachio, P, 2007-07-31 18:50:15 pAMPK inactivates ACC2 inhibiting malonyl-CoA synthesis Conversion of palmitic acid to palmitoyl-CoA Formation of Malonyl-CoA from Acetyl-CoA (muscle) Activation of cytosolic AMPK by phosphorylation PathwayStep89 PathwayStep93 PathwayStep86 PathwayStep88 PathwayStep87