Park E A, Cook G A
Department of Pharmacology, College of Medicine, The University of Tennessee, Memphis-The Health Science Center, 38163, USA.
Mol Cell Biochem. 1998 Mar;180(1-2):27-32.
Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating cardiac fatty acid oxidation which provides the primary source of energy for cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty acids into mitochondria and is recognized as the primary rate controlling step in fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation of fatty acid oxidation rates depends on both short-term regulation of enzyme activity and long-term regulation of enzyme synthesis. Most early investigations into metabolic control of fatty acid oxidation at the CPT-I step concentrated on the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not been found to undergo any alteration of its sensitivity. Short-term control of activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney, brain and most other tissues while muscle CPT-I is the sole isoform expressed in skeletal muscle as well as white and brown adipocytes. The heart is unique in that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed in the fetal heart, but at birth its activity begins to decline whereas the muscle isoform, which is very low at birth, becomes the predominant enzyme during postnatal development. In this paper, the differential regulation of the two CPT-I isoforms at the protein and the gene level will be discussed.
肉碱棕榈酰转移酶-I（CPT-I）在调节心脏脂肪酸氧化过程中起着关键作用，心脏脂肪酸氧化为心肌收缩提供了主要能量来源。CPT-I催化长链脂肪酸转运至线粒体，被认为是脂肪酸氧化的主要限速步骤。分子克隆技术已证明存在两种CPT-I同工型，分别由编码“肌肉”和“肝脏”酶的基因产生。脂肪酸氧化速率的调节既取决于酶活性的短期调节，也取决于酶合成的长期调节。大多数早期关于CPT-I步骤中脂肪酸氧化代谢控制的研究集中在肝脏酶上，该酶可被丙二酰辅酶A抑制，并且其对丙二酰辅酶A抑制的敏感性可发生显著增强或降低。肌肉CPT-I对丙二酰辅酶A抑制本质上更敏感，但尚未发现其敏感性有任何改变。肌肉CPT-I活性的短期控制显然受丙二酰辅酶A浓度的调节，以响应燃料供应（葡萄糖、乳酸、丙酮酸和酮体）。肝脏同工型是肝脏、肾脏、大脑和大多数其他组织线粒体中唯一存在的CPT-I酶，而肌肉CPT-I是骨骼肌以及白色和棕色脂肪细胞中表达的唯一同工型。心脏的独特之处在于它同时含有肌肉和肝脏同工型。肝脏CPT-I在胎儿心脏中高度表达，但在出生时其活性开始下降，而出生时很低的肌肉同工型在出生后发育过程中成为主要酶。本文将讨论两种CPT-I同工型在蛋白质和基因水平上的差异调节。
