Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake.

Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake.
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DOI:
10.1007/s11064-008-9833-3
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发表时间:
2009-05
影响因子:
4.4
通讯作者:
Ueda, Tetsufumi
Ueda, Tetsufumi
中科院分区:
医学3区
文献类型:
--
作者:
Ishida, Atsuhiko;Noda, Yasuko;Ueda, Tetsufumi

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Glucose metabolism is essential for normal brain function and plays a vital role in synaptic transmission. Recent evidence suggests that ATP synthesized locally by glycolysis, particularly via glyceraldehyde 3-phosphate dehydrogenase/3-phosphoglycerate kinase, is critical for synaptic transmission. We present evidence that ATP generated by synaptic vesicle-associated pyruvate kinase is harnessed to transport glutamate into synaptic vesicles. Isolated synaptic vesicles incorporated [3H]glutamate in the presence of phosphoenolpyruvate (PEP) and ADP. Pyruvate kinase activators and inhibitors stimulated and reduced PEP/ADP-dependent glutamate uptake, respectively. Membrane potential was also formed in the presence of pyruvate kinase activators. “ATP-trapping” experiments using hexokinase and glucose suggest that ATP produced by vesicle-associated pyruvate kinase is more readily used than exogenously added ATP. Other neurotransmitters such as GABA, dopamine, and serotonin were also taken up into crude synaptic vesicles in a PEP/ADP-dependent manner. The possibility that ATP locally generated by glycolysis supports vesicular accumulation of neurotransmitters is discussed.
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