2-溴软脂酸及其辅酶A和肉碱酯对线粒体脂肪酸氧化的特异性抑制作用。
Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its coenzyme A and carnitine esters.
作者信息
Chase J F, Tubbs P K
出版信息
Biochem J. 1972 Aug;129(1):55-65. doi: 10.1042/bj1290055.
Abstract
- The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain beta-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ;sink' for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.
摘要
- 2-溴软脂酸的辅酶A酯和肉碱酯是线粒体脂肪酸氧化极为强效且特异的抑制剂。2. 直接添加的2-溴软脂酰辅酶A或由2-溴软脂酸形成的2-溴软脂酰辅酶A，可抑制完整肝线粒体中肉碱依赖性的软脂酸或软脂酰辅酶A的氧化，但不抑制软脂酰肉碱的氧化。3. 2-溴软脂酰肉碱可抑制软脂酰肉碱以及软脂酸或软脂酰辅酶A的氧化。它对琥珀酸氧化无影响，但抑制丙酮酸、2-氧代戊二酸或己酸的氧化；不过，这些底物（但不包括软脂酸、软脂酰辅酶A或软脂酰肉碱）的氧化可通过肉碱恢复。4. 在受损的线粒体中，添加的2-溴软脂酰辅酶A确实会抑制软脂酰肉碱的氧化；丙酮酸氧化单独不受该抑制剂影响，但随后添加软脂酰肉碱时会受到损害。5. 研究结果如下解释。2-溴软脂酰辅酶A（以肉碱依赖性方式）使一组可被外部酰基辅酶A作用的肉碱软脂酰转移酶失活。这导致软脂酸或软脂酰辅酶A氧化受到抑制。完整线粒体中添加的酰基辅酶A无法作用的另一组肉碱软脂酰转移酶，可从外部2-溴软脂酰肉碱在基质内生成溴软脂酰辅酶A；该反应是可逆的。这种内部的2-溴软脂酰辅酶A使长链β-氧化失活（如果线粒体受损，添加的2-溴软脂酰辅酶A也会如此），其形成还会隔离线粒体内的辅酶A。由于该辅酶A由丙酮酸和2-氧代戊二酸脱氢酶共用，它们底物的氧化会因2-溴软脂酰肉碱而受到抑制，除非有游离肉碱可作为长链酰基的“汇”。6. 将这些效应与其他脂肪酸氧化抑制剂的报道效应进行了比较。
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本文引用的文献
1
Steady-state concentrations of coenzyme A, acetyl-coenzyme A and long-chain fatty acyl-coenzyme A in rat-liver mitochondria oxidizing palmitate.在氧化棕榈酸酯的大鼠肝脏线粒体中辅酶A、乙酰辅酶A和长链脂肪酰辅酶A的稳态浓度。
Biochem J. 1965 Nov;97(2):587-94. doi: 10.1042/bj0970587.
2
3
CARNITINE IN INTERMEDIARY METABOLISM. THE BIOSYNTHESIS OF PALMITYLCARNITINE BY CELL SUBFRACTIONS.肉碱在中间代谢中的作用。细胞亚组分合成棕榈酰肉碱的过程。
J Biol Chem. 1963 Aug;238:2774-9.
4
Properties of partially purified carnitine acetyltransferase.部分纯化的肉碱乙酰转移酶的特性
J Biol Chem. 1963 Jul;238:2509-17.
5
6
Studies on alpha-ketoglutaric oxidase. II. Purification and properties.α-酮戊二酸氧化酶的研究。II. 纯化及性质
J Biol Chem. 1952 May;197(2):851-62.
7
Removal of fatty acids from serum albumin by charcoal treatment.通过活性炭处理从血清白蛋白中去除脂肪酸。
J Biol Chem. 1967 Jan 25;242(2):173-81.
8
The partial latency and intramitochondrial distribution of carnitine-palmitoyltransferase (e.c.2.3.1.-), and the CoASH and carnitine permeable space of rat liver mitochondria.肉碱-棕榈酰转移酶（酶编号2.3.1.-）的部分潜伏期及线粒体内分布，以及大鼠肝脏线粒体的辅酶A和肉碱通透空间。
Biochem Biophys Res Commun. 1966 May 25;23(4):460-5. doi: 10.1016/0006-291x(66)90750-9.
9
Effects of 4-pentenoic acid on carbohydrate metabolism in pigeon liver homogenate.4-戊烯酸对鸽肝匀浆碳水化合物代谢的影响。
J Biol Chem. 1969 Mar 10;244(5):1212-9.
10
Apparent reversal of insulin resistance in cardiac muscle in alloxan-diabetes by 2-bromostearate.2-溴硬脂酸盐可使四氧嘧啶糖尿病心肌中的胰岛素抵抗明显逆转。
Nature. 1969 Feb 22;221(5182):777. doi: 10.1038/221777a0.
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