TY - GEN
T1 - Regulation of cytosolic and mitochondrial oxidation via malate-aspartate shuttle
T2 - An observation using dynamic 13C NMR spectroscopy
AU - Lu, Ming
AU - Banerjee, Suhanti
AU - Saidel, Gerald M.
AU - Yu, Xin
PY - 2011/8/18
Y1 - 2011/8/18
N2 - The malate-aspartate (M-A) shuttle provides an important mechanism of metabolic communication between the cytosol and the mitochondria. In this study, dynamic 13C NMR spectroscopy was combined with a multi-domain model of cardiacmetabolism for direct quantification ofmetabolic fluxes through the tricarboxylic acid (TCA) cycle (VTCA) and the M-Ashuttle (V M-A) in intact heart. The sensitivity of this approach to altered M-A shuttle activity was examined at different cytosolic redox states. Dynamic 13C NMR spectra were acquired from isolated rat hearts perfused with 13C 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.
AB - The malate-aspartate (M-A) shuttle provides an important mechanism of metabolic communication between the cytosol and the mitochondria. In this study, dynamic 13C NMR spectroscopy was combined with a multi-domain model of cardiacmetabolism for direct quantification ofmetabolic fluxes through the tricarboxylic acid (TCA) cycle (VTCA) and the M-Ashuttle (V M-A) in intact heart. The sensitivity of this approach to altered M-A shuttle activity was examined at different cytosolic redox states. Dynamic 13C NMR spectra were acquired from isolated rat hearts perfused with 13C 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.
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U2 - 10.1007/978-1-4419-7756-4_25
DO - 10.1007/978-1-4419-7756-4_25
M3 - Conference contribution
C2 - 21445786
AN - SCOPUS:84934441350
SN - 9781441977557
VL - 701
T3 - Advances in Experimental Medicine and Biology
SP - 185
EP - 192
BT - Oxygen Transport to Tissue XXXII
PB - Springer New York LLC
ER -