The hypolipidemic peroxisome-proliferating drug, bis(carboxymethylthio)-1.10 decane, a dicarboxylic metabolite of tiadenol, is activated to an acylcoenzyme A thioester.
The hypolipidemic peroxisome-proliferating drug, bis(carboxymethylthio)-1.10 decane, a dicarboxylic metabolite of tiadenol, is activated to an acylcoenzyme A thioester.
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降血脂过氧化物酶体增殖药物双（羧甲硫基）-1.10 癸烷（tiadenol 的二羧酸代谢物）被激活为酰基辅酶 A 硫酯。
DOI：
10.1016/0304-4165(90)90009-l
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
N. Aarsaether
中科院分区：
文献类型：
--
作者：
A. Aarsland;R. Berge;J. Bremer;N. Aarsaether
双（羧甲硫基）-1.10癸烷（BCMTD）是一种硫代二羧酸，具有降低血清总甘油三酯和胆固醇、诱导肝肿大、增加过氧化物酶体β-氧化和过氧化氢酶活性以及多细胞器定位酶：棕榈酰辅酶A合成酶、棕榈酰辅酶A水解酶、甘油磷酸酰基转移酶的活性等作用，是一种降血脂的过氧化物酶体增殖药物。（d）降低肉毒碱棕榈酰转移酶和尿酸氧化酶的活性;（e）诱导过氧化物酶体中的双功能壬基辅酶A水合酶。本研究证实了噻腺醇给药对雄性大鼠肝脏脂肪酸代谢关键酶活性的影响。然而，肝脏多效性反应更显着的二羧酸比其醇。在一项单独的剂量-反应研究中，发现BCMTD是比噻腺苷醇更有效的过氧化物酶体β-氧化诱导剂。BCMTD可以在体外通过二羧基-CoA合成酶活化成其辅酶A硫酯。在对照组和BMCTD处理的动物中，除胞质外，在所有细胞组分中均发现合成酶活性。过氧化物酶体增殖药物的酰基-CoA硫酯是否可能是过氧化物酶体增殖的介质，应予以考虑。
Bis(carboxymethylthio)-1.10 decane (BCMTD), a thiodicarboxylic acid, was shown to be a hypolipidemic peroxisome-proliferating drug as it: (a) decreased the total serum triacylglycerols and cholesterol; (b) induced hepatomegaly; (c) increased the peroxisomal β-oxidation and catalase activity and the activities of the multiorganelle localized enzymes: palmitoyl-CoA synthetase, palmitoyl-CoA hydrolase, glycerophosphate acyltransferase; (d) decreased the carnitine palmitoyltransferase and urate oxidase activities; and (e) induced the bifunctional eonyl-CoA hydratase in peroxisomes. The present study has confirmed the effect of tiadenol administration on the activities of key enzymes involved in hepatic fatty acid metabolism in male rats. However, the hepatic pleiotropic response was more marked with the dicarboxylic acid than with its alcohol. In a separate dose-response study BCMTD was found to be a more potent inducer of peroxisomal β-oxidation compared to tiadenol. BCMTD can be activated in vitro to its coenzyme A thioester by a dicarboxyl-CoA synthetase. In control and BMCTD-treated animals, the synthetase activity was found in all cullular fractions except the cytosolic. Whether the acyl-CoA thioesters of peroxisome-proliferating drugs may be mediators of peroxisomal proliferation should be considered.
降血脂剂氯贝特快速诱导小鼠肝脏甘油磷酸酰基转移酶。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Das,AK;Aquilina,JW;Hajra,AK
通讯作者：
Hajra,AK