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4.1 Cytoplasmic Glycolytic Enzymes. Synaptic Vesicle-Associated Glycolytic ATP-Generating Enzymes: Coupling to Neurotransmitter Accumulation

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Glucose metabolism is of paramount importance in synaptic transmission and brain function, providing the major cerebral energy source. Yet, under hypoglycemic conditions in which abnormal synaptic transmission and pathophysiological behavior are observed, averaged cellular ATP levels are barely altered. Investigations into this apparent paradox led to the discovery in synaptic vesicles of the glycolytic ATP-generating enzymes glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase; these enzymes, when activated, are capable of supporting uptake into synaptic vesicles of the major excitatory neurotransmitter glutamate. This represents the first evidence for coupling between glycolysis and neurotransmitter transport into synaptic vesicles. Further studies have shown that glycolytically produced ATP, rather than ATP synthesized in mitochondria, plays a major role in accumulating glutamate within synaptic vesicles in synaptosomes (pinched-off nerve ending preparation). These lines of evidence could provide fresh insight into the essential nature of glycolysis in synaptic transmission. It is argued that the locally produced ATP on the surface of synaptic vesicles by glycolytic enzymes is preferentially harnessed to rapidly refill emptied synaptic vesicles with neurotransmitters. A variety of evidence is briefly reviewed, which indicates that glycolysis is also coupled to the transport of other cations, namely Na+, K+ and Ca2+. It is proposed that subcellular local glycolytic synthesis of ATP plays a crucial role in meeting rapid energy demand for various speedy cellular processes.

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Abbreviations

4-AP:

4-aminopyridine

1,3-BPG:

1,3-bisphosphoglycerate

GAP:

glyceraldehyde-3-phosphate

3-PG:

3-phosphoglycerate

GABA:

γ-aminobutyric acid

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

3-PGK:

3-phosphoglycerate kinase

PK:

pyruvate kinase

VGLUT:

vesicular glutamate transporter

PSD:

postsynaptic density

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Acknowledgments

This work was supported by National Institutes of Health Grant NS 42200 (TU). We thank Mary Roth and Judy Ueda for excellent assistance in preparation of the manuscript.

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  1. T. Ueda
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  2. A. Ikemoto
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA

    Gary E. Gibson Ph.D. (Professor of Neuroscience Department of Neurology and Neuroscience) (Professor of Neuroscience Department of Neurology and Neuroscience)

  3. Dept. Neurology and Physiology & Biophysics, University Arkansas for Medical Sciences, Shorey Bldg. Room 715, Mail Slot 830 4301 W. Markham St., Little Rock, AR, 72205, USA

    Gerald A. Dienel Ph.D. (Professor) (Professor)

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Ueda, T., Ikemoto, A. (2007). 4.1 Cytoplasmic Glycolytic Enzymes. Synaptic Vesicle-Associated Glycolytic ATP-Generating Enzymes: Coupling to Neurotransmitter Accumulation. In: Lajtha, A., Gibson, G.E., Dienel, G.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30411-3_10

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