Berge R K, Aarsland A
Biochim Biophys Acta. 1985 Nov 14;837(2):141-51. doi: 10.1016/0005-2760(85)90237-1.
Data obtained in earlier studies with rats fed diets containing high doses of peroxisome proliferators (niadenate, tiadenol, clofibrate, or nitotinic acid) are used to look for a quantitative relationship between peroxisomal beta-oxidation, palmitoyl-CoA hydrolase, palmitoyl-CoA synthetase and carnitine palmitoyltransferase activities, and the cellular concentration of their substrate and reaction products. The order of the hyperlipidemic drugs with regard to their effect on CoA derivatives and enzyme activities was niadenate greater than tiadenol greater than clofibrate greater than nicotinic acid. Linear regression analysis of long-chain acyl-CoA content versus palmitoyl-CoA hydrolase and peroxisomal beta-oxidation activity showed highly significant linear correlations both in the total liver homogenate and in the peroxisome-enriched fractions. A dose-response curve of tiadenol showed that carnitine palmitoyltransferase and palmitoyl-CoA synthetase activities and the ratio of long-chain acyl-CoA to free CoASH in total homogenate rose at low doses before detectable changes occurred in the peroxisomal beta-oxidation and palmitoyl-CoA hydrolase activity. A plot of this ratio parallelled the palmitoyl-CoA synthetase activity. The specific activity of microsomally localized carnitine palmitoyl-transferase was low and unchanged up to a dose where no enhanced peroxisomal beta-oxidation was observed, but over this dose the activity increased considerably so that the specific of the enzyme in the mitochondrial and microsomal fractions became comparable. The mitochondrial palmitoyl-CoA synthetase activity decreased gradually. The correlations may be interpreted as reflecting a common regulation mechanism for palmitoyl-CoA hydrolase and peroxisomal beta-oxidation enzymes, i.e., the cellular level of long-chain acyl-CoA acting as the metabolic message for peroxisomal proliferation resulting in induction of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase activity. The findings are discussed with regard to their possible consequences for mitochondrial fatty acid oxidation and the conversion of long-chain acyl-L-carnitine to acyl-CoA derivatives.
早期对喂食含高剂量过氧化物酶体增殖剂（尼阿地酯、替阿地诺、氯贝丁酯或烟酸）日粮的大鼠进行研究所获得的数据，用于探寻过氧化物酶体β-氧化、棕榈酰辅酶A水解酶、棕榈酰辅酶A合成酶和肉碱棕榈酰转移酶活性与其底物及反应产物的细胞浓度之间的定量关系。就高脂血症药物对辅酶A衍生物和酶活性的影响而言，其顺序为尼阿地酯大于替阿地诺大于氯贝丁酯大于烟酸。长链酰基辅酶A含量与棕榈酰辅酶A水解酶及过氧化物酶体β-氧化活性的线性回归分析表明，在全肝匀浆和富含过氧化物酶体的组分中均呈现高度显著的线性相关性。替阿地诺的剂量反应曲线显示，在过氧化物酶体β-氧化和棕榈酰辅酶A水解酶活性出现可检测变化之前，全匀浆中的肉碱棕榈酰转移酶和棕榈酰辅酶A合成酶活性以及长链酰基辅酶A与游离辅酶A的比值在低剂量时就已升高。该比值的曲线与棕榈酰辅酶A合成酶活性平行。微粒体定位的肉碱棕榈酰转移酶的比活性较低，在未观察到过氧化物酶体β-氧化增强的剂量范围内保持不变，但超过该剂量后，活性显著增加，以至于线粒体和微粒体组分中该酶的比活性变得相当。线粒体棕榈酰辅酶A合成酶活性逐渐降低。这些相关性可解释为反映了棕榈酰辅酶A水解酶和过氧化物酶体β-氧化酶的共同调节机制，即长链酰基辅酶A的细胞水平作为过氧化物酶体增殖的代谢信号，导致过氧化物酶体β-氧化和棕榈酰辅酶A水解酶活性的诱导。本文就这些发现对线粒体脂肪酸氧化以及长链酰基-L-肉碱向酰基辅酶A衍生物转化的可能影响进行了讨论。
