Neurochemical Research

, Volume 37, Issue 12, pp 2731–2737

Enhanced Glutamate Uptake into Synaptic Vesicles Fueled by Vesicle-generated ATP from Phosphoenolpyruvate and ADP

Proposed Role of a Novel Enzyme
Original Paper

DOI: 10.1007/s11064-012-0864-4

Cite this article as:
Takeda, K. & Ueda, T. Neurochem Res (2012) 37: 2731. doi:10.1007/s11064-012-0864-4


Glycolytic ATP synthesis by synaptic vesicles provides an efficient mechanism for fueling vesicular loading of the neurotransmitter glutamate. This is achieved in part by vesicle-bound pyruvate kinase. However, we have found that vesicular glutamate uptake, in the presence of the pyruvate kinase substrates ADP and phosphoenolpyruvate (PEP), substantially exceeds that caused by exogenous ATP. We propose that this much enhanced uptake is in part due to extra ATP produced via a mechanism involving a novel enzyme, PEP-dependent ADP synthase. We discuss implications for this enzyme in energy homeostasis and pathophysiology, as well as in efficient synaptic glutamate transmission.


Energy metabolism ADP synthesis Glycolytic intermediate VGLUT Glutamate transmission 





High pressure liquid chromatography


Adenosine 5′-O-thiomonophosphate

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Molecular and Behavioral Neuroscience Institute, Medical SchoolThe University of MichiganAnn ArborUSA
  2. 2.Department of Pharmacology, Medical SchoolThe University of MichiganAnn ArborUSA
  3. 3.Department of Psychiatry, Medical SchoolThe University of MichiganAnn ArborUSA
  4. 4.Department of EducationTokyo University of AgricultureTokyoJapan
  5. 5.Molecular and Behavioral Neuroscience InstituteThe University of MichiganAnn ArborUSA

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