Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation

Malonyl-CoA is a potent inhibitor of fatty acid uptake into the mitochondri a. Although the synthesis of malonyl-CoA in the heart by acetyl-CoA carboxy lase (ACC) has been well characterized, no information is available as to h ow malonyl-CoA is degraded. We demonstrate that malonyl-CoA decarboxylase ( MCD) activity is present in the heart. Partial purification revealed a prot ein of similar to 50 kDa. The role of MCD in regulating fatty acid oxidatio n was also studied using isolated, perfused hearts from newborn rabbits and adult rats. Fatty acid oxidation in rabbit hearts increased dramatically b etween 1 day and 7 days after birth, which was accompanied by a decrease in both ACC activity and malonyl-CoA levels and a parallel increase in MCD ac tivity. When adult rat hearts were aerobically reperfused after a 30-min pe riod of no-flow ischemia, levels of malonyl-CoA decreased dramatically, whi ch was accompanied by a decrease in ACC activity, a maintained MCD activity , and an increase in fatty acid oxidation rates. Taken together, our data s uggest that the heart has an active MCD that has an important role in regul ating fatty acid oxidation rates.