Dyck J R, Barr A J, Barr R L, Kolattukudy P E, Lopaschuk G D
Cardiovascular Research and Lipid Lipoprotein Research Groups, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Am J Physiol. 1998 Dec;275(6):H2122-9. doi: 10.1152/ajpheart.1998.275.6.H2122.
Malonyl-CoA is a potent inhibitor of fatty acid uptake into the mitochondria. Although the synthesis of malonyl-CoA in the heart by acetyl-CoA carboxylase (ACC) has been well characterized, no information is available as to how malonyl-CoA is degraded. We demonstrate that malonyl-CoA decarboxylase (MCD) activity is present in the heart. Partial purification revealed a protein of approximately 50 kDa. The role of MCD in regulating fatty acid oxidation was also studied using isolated, perfused hearts from newborn rabbits and adult rats. Fatty acid oxidation in rabbit hearts increased dramatically between 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 activity. When adult rat hearts were aerobically reperfused after a 30-min period of no-flow ischemia, levels of malonyl-CoA decreased dramatically, which was accompanied by a decrease in ACC activity, a maintained MCD activity, and an increase in fatty acid oxidation rates. Taken together, our data suggest that the heart has an active MCD that has an important role in regulating fatty acid oxidation rates.
丙二酰辅酶A是脂肪酸进入线粒体的强效抑制剂。虽然乙酰辅酶A羧化酶（ACC）在心脏中合成丙二酰辅酶A的过程已得到充分表征，但关于丙二酰辅酶A如何降解尚无相关信息。我们证明心脏中存在丙二酰辅酶A脱羧酶（MCD）活性。部分纯化显示有一种约50 kDa的蛋白质。还使用新生兔和成年大鼠的离体灌注心脏研究了MCD在调节脂肪酸氧化中的作用。兔心脏中的脂肪酸氧化在出生后1天至7天之间显著增加，同时ACC活性和丙二酰辅酶A水平降低，而MCD活性则平行增加。当成年大鼠心脏在30分钟无血流缺血后进行有氧再灌注时，丙二酰辅酶A水平显著降低，同时ACC活性降低，MCD活性保持不变，脂肪酸氧化速率增加。综上所述，我们的数据表明心脏具有活跃的MCD，其在调节脂肪酸氧化速率中起重要作用。
