Molecular & Behavioral Neuroscience Institute, Medical School, The University of Michigan, Ann Arbor, Michigan, USA.
J Neurochem. 2012 Apr;121(2):184-96. doi: 10.1111/j.1471-4159.2012.07684.x. Epub 2012 Mar 13.
Synaptic vesicle loading of glutamate is a pivotal step in glutamate synaptic transmission. The molecular machinery responsible for this step is comprised of v-type proton-pump ATPase and a vesicular glutamate transporter. Recent evidence indicates that synaptic vesicles are endowed with glycolytic ATP-synthesizing enzymes, providing energy for immediate use by vesicle-bound proton-pump ATPase. In this study, we provide evidence that synaptic vesicles are also capable of synthesizing the vesicular glutamate transporter substrate glutamate, from α-ketoglutarate and l-aspartate (as the amino group donor); glutamate thus produced is taken up into vesicles. We also report a finding that α-ketoglutarate-derived glutamate uptake into synaptic vesicles and aspartate aminotransferase are inhibited by 2,3-pyrazinedicarboxylate. Evidence is given that this is a selective inhibitor for aspartate aminotransferase. These observations provide insight into understanding the nerve endings' mechanism for high efficiency in glutamate transmission. Finding this inhibitor may have implications for further experimentation on the role of α-ketoglutarate-derived glutamate in glutamate transmission.
谷氨酸囊泡的装载是谷氨酸突触传递的关键步骤。负责这一步骤的分子机制包括 v 型质子泵 ATP 酶和囊泡谷氨酸转运体。最近的证据表明，突触囊泡具有糖酵解 ATP 合成酶，为囊泡结合的质子泵 ATP 酶提供即时使用的能量。在这项研究中，我们提供的证据表明，突触囊泡也能够从α-酮戊二酸和 l-天冬氨酸（作为氨基供体）合成囊泡谷氨酸转运体的底物谷氨酸；由此产生的谷氨酸被摄取到囊泡中。我们还报告了一个发现，即 2,3-吡嗪二羧酸抑制突触囊泡中α-酮戊二酸衍生的谷氨酸摄取和天冬氨酸转氨酶。有证据表明，这是天冬氨酸转氨酶的选择性抑制剂。这些观察结果为理解神经末梢在谷氨酸传递中高效的机制提供了新的认识。发现这种抑制剂可能对进一步研究α-酮戊二酸衍生的谷氨酸在谷氨酸传递中的作用具有重要意义。
