Induction of rat liver mitochondrial fatty acid elongation by the administration of peroxisome proliferator di-(2-ethylhexyl)phthalate: absence of elongation activity in peroxisomes.
Induction of rat liver mitochondrial fatty acid elongation by the administration of peroxisome proliferator di-(2-ethylhexyl)phthalate: absence of elongation activity in peroxisomes.
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通过给予过氧化物酶体增殖剂邻苯二甲酸二（2-乙基己基）酯诱导大鼠肝脏线粒体脂肪酸伸长：过氧化物酶体中缺乏伸长活性。
DOI：
10.1016/0003-9861(86)90437-6
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发表时间：
1986
影响因子：
3.9
通讯作者：
Cinti,DL
中科院分区：
文献类型：
--
作者：
Nagi,MN;Cook,L;Ghesquier,D;Cinti,DL
对雄性Sprague-Dawley大鼠给予邻苯二甲酸二（2-乙基己基）酯（DEHP）3导致乙酰辅酶A依赖性肝线粒体脂肪酸延长活性增加3倍以上。从对照组或DEHP处理的大鼠中获得的过氧化物酶体不能延长任何测试的脂肪酰辅酶A。此外，过氧化物酶体具有非反式-2-烯酰辅酶A还原酶活性。因此，对照组和DEHP喂养动物的7500 g级分中的延伸活性可以完全归因于线粒体。最大的乙酰辅酶A的掺入发生在NADH和NADPH的存在下，辛酰辅酶A（8：0）和癸酰辅酶A（10：0）被认为是最佳的引物脂肪酸延长在对照组和DEHP处理的动物。两组动物中8：0 CoA的表观Km均为17 μM，而处理后Vmax从4.5 nmol/min/mg增加至12.5 nmol/min/mg。在对照组和DEHP处理组中，10：0 CoA的表观Km均为10 μM，而表观Vmax从2.5增加至10 nmol/min/mg;棕榈酰-CoA（16：0）是链延长的非常差的引物。虽然乙酰辅酶A依赖性脂肪酸的延长被DEHP处理刺激，但乙醛反式-2-烯酰辅酶A还原酶活性不受影响。以8：0辅酶A为引物的DEHP处理后，线粒体总延伸活性比以反式-2-癸烯酰辅酶A（10：1）为引物的烯酰辅酶A还原酶活性高约2倍。这是中间体积累的结果，这些中间体被鉴定为astrans-2-10：1（35%）、β-羟基10：0（25%）、未鉴定的（15%）和伸长的饱和产物10：0（24%）。在对照组和DEHP处理组动物中均发现了一个醋酸盐单位的伸长率。结果进行了讨论的生理意义。
The administration of di-(2-ethylhexyl)phthalate (DEHP)3to male Sprague-Dawley rats resulted in more than a threefold increase in activity of acetyl CoA-dependent hepatic mitochondrial fatty acid elongation. Peroxisomes obtained either from control or DEHP-treated rats were not capable of elongating any of the fatty acyl CoAs tested. Furthermore, the peroxisomes possessed notrans-2-enoyl CoA reductase activity. Therefore, the elongation activity in the 7500gfraction from both control and DEHP-fed animals can be attributed totally to the mitochondria. Maximal incorporation of acetyl CoA occurred in the presence of both NADH and NADPH, and octanoyl CoA (8:0) and decanoyl CoA (10:0) were found to be optimal primers for fatty acid elongation in both control and DEHP-treated animals. The apparentKmfor 8:0 CoA was 17 μM in both animal groups while theVmaxwas increased from 4.5 to 12.5 nmol/min/mg following treatment. The apparentKmfor 10:0 CoA was 10 μM in both control and DEHP-treated groups while the apparentVmaxincreased from 2.5 to 10 nmol/min/mg; palmitoyl-CoA (16:0) was a very poor primer for chain elongation. Although the acetyl CoA-dependent fatty acid elongation was stimulated by DEHP treatment, the mitochondrialtrans-2-enoyl CoA reductase activity was unaffected. The mitochondrial total elongation activity following DEHP-treatment using 8:0 CoA as primer was about two times higher than enoyl CoA reductase activity usingtrans-2-decenoyl CoA (10:1). This was the result of accumulation of intermediates, which were identified astrans-2-10:1 (35%), β-hydroxy 10:0 (25%), unidentified (15%), and elongated saturated product 10:0 (24%). Elongation by one acetate unit was found in both the control and DEHP-treated animals. The results are discussed in terms of physiological significance.