通过苹果酸-天冬氨酸穿梭作用调节细胞质和线粒体氧化：使用动态 ¹³C NMR 光谱的观察。
Regulation of cytosolic and mitochondrial oxidation via malate-aspartate shuttle: an observation using dynamic ¹³C NMR spectroscopy.
机构信息
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
出版信息
Adv Exp Med Biol. 2011;701:185-92. doi: 10.1007/978-1-4419-7756-4_25.
The malate-aspartate (M-A) shuttle provides an important mechanism of metabolic communication between the cytosol and the mitochondria. In this study, dynamic (13)C NMR spectroscopy was combined with a multi-domain model of cardiac metabolism for direct quantification of metabolic fluxes through the tricarboxylic acid (TCA) cycle (VTCA) and the M-A shuttle (VM-A) in intact heart. The sensitivity of this approach to altered M-A shuttle activity was examined at different cytosolic redox states. Dynamic (13)C NMR spectra were acquired from isolated rat hearts perfused with (13)C labeled fatty acid at either low (fatty acid only) or high cytosolic redox state induced by exogenous glucose and lactate. VTCA and VM-A were determined by least-square fitting of the model to NMR data. Our results showed that while VTCA was similar, VM-A increased by 75% at high cytosolic redox state. Therefore, our proposed method provides the opportunity for direct quantification of metabolic communication between subcellular compartments via the M-A shuttle.
苹果酸-天冬氨酸（M-A）穿梭为细胞质和线粒体之间的代谢通讯提供了一个重要的机制。在这项研究中，动态（13）C NMR 光谱学与心脏代谢的多域模型相结合，用于直接定量通过三羧酸（TCA）循环（VTCA）和 M-A 穿梭（VM-A）的代谢通量在完整的心脏。在不同的细胞质氧化还原状态下，研究了这种方法对改变的 M-A 穿梭活性的敏感性。在低（仅脂肪酸）或高细胞质氧化还原状态下（由外源葡萄糖和乳酸诱导），用（13）C 标记的脂肪酸灌注分离的大鼠心脏，并从其获得动态（13）C NMR 光谱。通过将模型拟合到 NMR 数据来确定 VTCA 和 VM-A。我们的结果表明，虽然 VTCA 相似，但在高细胞质氧化还原状态下，VM-A 增加了 75％。因此，我们提出的方法为通过 M-A 穿梭直接定量细胞内区室之间的代谢通讯提供了机会。
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