Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart
Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart
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DOI：
10.1016/s0006-3495(02)75369-1
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发表时间：
2002-01-01
影响因子：
3.4
通讯作者：
Lewandowski, ED
中科院分区：
文献类型：
--
作者：
O'Donnell, JM;Alpert, NM;Lewandowski, ED
长链脂肪酸（LCFA）转运的协调：穿过线粒体膜（V-PAL），随后通过β-氧化和三羧酸（TCA）循环（V-toa）的氧化速率一直难以在完整的心脏中表征。动态C-13-NMR的动力学分析区分这些流量率在离体兔心脏。在9.4 T磁体中用0.5 mM [2，4，6，8，10，12，14，16-C-13（8）]棕榈酸盐（n = 4）或0.5 mM C-13标记的棕榈酸盐加0.08 mM未标记的丁酸盐（n = 4）灌注心脏。丁酸是一种短链脂肪酸（SCFA），其绕过线粒体的LCFA转运蛋白。在单独氧化棕榈酸的心脏中，V-TCA与V-PAL的比例为8：1。这与一个棕榈酸分子产生八个乙酰辅酶A分子用于随后通过TCA循环的氧化一致。丁酸盐的添加提高了该比率;由于SCFA诱导的V-TCA增加43%（p < 0.05），V-TCA/V-PAL = 12：1。然而，SCFA氧化并没有显著减少棕榈酸盐转运到线粒体中：V-PAL = 1.0 +/- 0.2 μ mol/min/g dw，单独使用棕榈酸盐，而棕榈酸盐加丁酸盐为0.9 +/- 0.1。因此，β-氧化的产物优先被引导到TCA循环，远离线粒体流出通过肉毒碱乙酰转移酶。
The coordination of long chain fatty acid (LCFA) transport: across the mitochondrial membrane (V-PAL) with subsequent oxidation rate through beta-oxidation and the tricarboxylic acid (TCA) cycle (V-toa) has been difficult to characterize in the intact heart. Kinetic analysis of dynamic C-13-NMR distinguished these flux rates in isolated rabbit hearts. Hearts were perfused in a 9.4 T magnet with either 0.5 mM [2,4,6,8,10,12,14,16-C-13(8)] palmitate (n = 4), or 0.5 mM C-13-labeled palmitate plus 0.08 mM unlabeled butyrate (n = 4). Butyrate is a short chain fatty acid (SCFA) that bypasses the LCFA transporters of mitochondria. In hearts oxidizing palmitate alone, the ratio of V-TCA to V-PAL was 8:1. This is consistent with one molecule of palmitate yielding eight molecules of acetyl-CoA for the subsequent oxidation through the TCA cycle. Addition of butyrate elevated this ratio; V-TCA/V-PAL = 12:1 due to an SCFA-induced increase in V-TCA of 43% (p < 0.05). However, SCFA oxidation did not significantly reduce palmitate transport into the mitochondria: V-PAL = 1.0 +/- 0.2 mu mol/min/g dw with palmitate alone versus 0.9 +/- 0.1 with palmitate plus butyrate. Thus, the products of beta-oxidation are preferentially channeled to the TCA cycle, away from mitochondrial efflux via carnitine acetyltransferase.