High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5′-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase

摘要: We determined whether high fatty acid oxidation rates during aerobic reperfusion of ischemic hearts could be explained by a decrease in malonyl-CoA levels, which would relieve inhibition carnitine palmitoyl-transferase 1, the rate-limiting enzyme involved mitochondrial uptake acids. Isolated working rat perfused with 1.2 mM palmitate were subjected to 30 min global ischemia, followed 60 reperfusion. Fatty 136% higher than seen aerobically control hearts, despite fact that cardiac work recovered only 16% pre-ischemic values. Neither activity palmitoyltransferase or IC50 value for 1 altered mitochondria isolated from aerobic, ischemic, reperfused hearts. Levels extremely low at end compared levels controls, as was acetyl-CoA carboxylase, produces malonyl-CoA. The 5'-AMP-activated protein kinase, has been shown phosphorylate and inactivate carboxylase other tissues, significantly increased remained elevated throughout These results suggest accumulation 5'-AMP ischemia an activation AMP-activated phosphorylates inactivates ACC subsequent wil result accelerated