Carnitine-acylcarnitine translocase in ischemia: evidence for sulfhydryl modification.
Carnitine-acylcarnitine translocase in ischemia: evidence for sulfhydryl modification.
复制标题
缺血中的肉碱-酰基肉碱转位酶：巯基修饰的证据。
DOI：
10.1152/ajpheart.1987.253.6.h1557
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
McMillin,JB
中科院分区：
文献类型：
--
作者：
Pauly,DF;Yoon,SB;McMillin,JB
冠状动脉闭塞和回流后，碳水化合物的分解代谢增强，而脂肪酸的利用则延迟。为了验证缺血性心脏对脂肪酸的“震惊”反映了脂肪酸转运到线粒体的减少这一假设，我们检查了参与转运的两种活性：肉碱-酰基肉碱转位酶和肉碱棕榈酰转移酶 II (CPT II)。在从缺血性犬心脏（左回旋支闭塞 60 分钟）分离的线粒体中，易位酶的肉毒碱交换的最大速度降低了 55%。缺血心脏的线粒体显示总基质谷胱甘肽减少 50%，谷胱甘肽二硫化物 (GSSG) 增加 200%，还原型谷胱甘肽 (GSH) 与 GSSG 的比率下降 80%，这表明转位酶活性的丧失可能是蛋白质巯基修饰的结果。为了支持这一点，用巯基还原剂、谷胱甘肽或二硫苏糖醇处理这些线粒体，可以恢复肉毒碱交换的控制。缺血心肌再灌注 20 分钟后观察到线粒体 GSH 部分恢复和 GSSG 减少。再灌注时肉碱交换的持续抑制表明其他机制可能会阻止活性的恢复。转位酶上棕榈酰肉碱的导入与 CPT II 的棕榈酰辅酶 A 生产相结合。来自缺血心脏的耦合活性降低的线粒体也具有最低的棕榈酰肉碱支持的呼吸速率，这表明在严重缺血的组织中，易位-酯交换序列可能成为脂肪酸氧化的速率限制。
After coronary occlusion and reflow, carbohydrate catabolism is enhanced, whereas fatty acid utilization is delayed. To test the hypothesis that "stunning" of fatty acid use by ischemic heart reflects reduced fatty acid transport into the mitochondria, two activities involved in the transport were examined: carnitine-acylcarnitine translocase and carnitine palmitoyltransferase II (CPT II). The maximal velocity for carnitine exchange of the translocase is reduced 55% in mitochondria isolated from ischemic canine heart (60-min left circumflex occlusion). Mitochondria from ischemic heart show 50% depletion in total matrix glutathione, a 200% increase in glutathione disulfide (GSSG), and an 80% decrease in the ratio of reduced glutathione (GSH) to GSSG, suggesting that the loss of translocase activity may be a consequence of protein sulfhydryl modifications. In support of this, treatment of these mitochondria with the sulfhydryl-reducing agents, GSH or dithiothreitol, restores carnitine exchange to control. Partial return of mitochondrial GSH and a decrease in GSSG are observed with a 20-min reperfusion of the ischemic myocardium. Continued depression in carnitine exchange with reperfusion suggests that other mechanisms may prevent restoration of activity. Import of palmitoylcarnitine on the translocase is coupled to palmitoyl-CoA production by CPT II. Mitochondria from ischemic heart with decreased coupling activity also have the lowest palmitoylcarnitine-supported respiratory rates, suggesting that in severely ischemic tissue the translocation-transesterification sequence may become rate limiting to fatty acid oxidation.