Eacho P I, Foxworthy P S
Department of Biochemical Toxicology, Eli Lilly and Company, Greenfield, IN 46140.
Biochem Biophys Res Commun. 1988 Dec 30;157(3):1148-53. doi: 10.1016/s0006-291x(88)80993-8.
The acute effect of the hypolipidemic agent bezafibrate on fatty acid oxidation was studied in rat hepatocytes and mitochondria. Bezafibrate caused a concentration-related inhibition of oleate oxidation in liver cells. In mitochondria bezafibrate inhibited the oxidation of palmitoyl CoA but had no effect on palmitoylcarnitine oxidation, suggesting the site of inhibition was the formation of the carnitine derivative. Bezafibrate and bezafibroyl CoA inhibited the overt carnitine palmitoyltransferase (I) in rat liver mitochondria with comparable potency but with distinct kinetics. The inhibition caused by bezafibrate was not prevented by omission of Mg++-ATP from the assay mixture, indicating activation of bezafibrate to bezafibroyl CoA was not required for inhibition. The data demonstrate that bezafibrate, like several other peroxisome proliferating agents, inhibits mitochondrial fatty acid oxidation in rat liver. The inhibition may be relevant to the mechanism of peroxisome proliferation.
在大鼠肝细胞和线粒体中研究了降血脂药物苯扎贝特对脂肪酸氧化的急性作用。苯扎贝特对肝细胞中油酸氧化产生浓度相关的抑制作用。在线粒体中，苯扎贝特抑制棕榈酰辅酶A的氧化，但对棕榈酰肉碱氧化没有影响，这表明抑制位点是肉碱衍生物的形成。苯扎贝特和苯扎贝特辅酶A以相当的效力但不同的动力学抑制大鼠肝脏线粒体中明显的肉碱棕榈酰转移酶（I）。测定混合物中省略Mg++-ATP并不能阻止苯扎贝特引起的抑制作用，这表明抑制作用不需要苯扎贝特激活为苯扎贝特辅酶A。数据表明，苯扎贝特与其他几种过氧化物酶体增殖剂一样，抑制大鼠肝脏中的线粒体脂肪酸氧化。这种抑制作用可能与过氧化物酶体增殖的机制有关。
