Flux control exerted by mitochondrial outer membrane carnitine palmitoyltransferase over beta-oxidation, ketogenesis and tricarboxylic acid cycle activity in hepatocytes isolated from rats in different metabolic states
Flux control exerted by mitochondrial outer membrane carnitine palmitoyltransferase over beta-oxidation, ketogenesis and tricarboxylic acid cycle activity in hepatocytes isolated from rats in different metabolic states
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DOI：
10.1042/bj3170791
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发表时间：
1996-08-01
影响因子：
4.1
通讯作者：
Zammit, VA
中科院分区：
文献类型：
--
作者：
Drynan, L;Quant, PA;Zammit, VA
在从处于不同代谢状态（进食、24 h饥饿、饥饿-再进食和饥饿/胰岛素处理）的大鼠中分离的肝细胞中测量线粒体外膜肉毒碱棕榈酰转移酶（CPT I）相对于β-氧化、生酮和三羧酸循环活性的总体速率的通量控制系数。选择这些条件是因为存在关于CPT I何时停止对脂肪氧化速率施加显著控制的争议[Moir和Zammit（1994）Trends Biochem. Sci. 19，313-317]，这被转移到接近酰基肉毒碱合成的一个或多个步骤（例如减少脂肪酸向肝脏的递送）或由线粒体3-羟基-3-甲基戊二酰-CoA合酶催化的反应[Hegardt（1995）Biochem. Sec. Trans. 23，486-490]。因此，在本研究中使用分离的肝细胞来排除非酯化脂肪酸（NEFA）向肝脏递送速率变化的参与，例如体内发生的变化，并确定在NEFA恒定供应的条件下，CPT I是否保留对脂肪酸氧化为酮和二氧化碳的相关通量的控制，或者控制是否转移到另一个（肝细胞内）位点。结果清楚地表明，在所有研究条件下，CPT I相对于总体β-氧化和酮生成的通量控制系数都非常高，表明在研究的代谢转换期间，控制不会丢失到另一个肝内位点。CPT I对三羧酸循环活性的控制一直很低。这些研究结果的意义整合的脂肪酸和碳水化合物代谢在肝脏中进行了讨论。
The Flux Control Coefficients of mitochondrial outer membrane carnitine palmitoyltransferase (CPT I) with respect to the overall rates of beta-oxidation, ketogenesis and tricarboxylic acid cycle activity were measured in hepatocytes isolated from rats in different metabolic states (fed, 24 h-starved, starved-refed and starved/insulin-treated). These conditions were chosen because there is controversy as to whether, when significant control ceases to be exerted by CPT I over the rate of fatty oxidation [Moir and Zammit (1994) Trends Biochem. Sci. 19, 313-317], this is transferred to one or more steps proximal to acylcarnitine synthesis (e.g. decreased delivery of fatty acids to the liver) or to the reaction catalysed by mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase [Hegardt (1995) Biochem. Sec. Trans. 23, 486-490]. Therefore isolated hepatocytes were used in the present study to exclude the involvement of changes in the rate of delivery of non-esterified fatty acids (NEFA) to the liver, such as occur in vivo, and to ascertain whether, under conditions of constant supply of NEFA, CPT I retains control over the relevant fluxes of fatty acid oxidation to ketones and carbon dioxide, or whether control is transferred to another (intrahepatocytic) site. The results clearly show that the Flux Control Coefficients of CPT I with respect to overall beta-oxidation and ketogenesis are very high under all conditions investigated, indicating that control is not lost to another intrahepatic site during the metabolic transitions studied. The control of CPT I over tricarboxylic acid cycle activity was always very low. The significance of these findings for the integration of fatty acid and carbohydrate metabolism in the liver is discussed.