Enhanced glutamate uptake into synaptic vesicles fueled by vesicle-generated ATP from phosphoenolpyruvate and ADP. Proposed role of a novel enzyme.
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.
Molecular and Behavioral Neuroscience Institute, Medical School, The University of Michigan, 109 Zina Pitcher, Ann Arbor, MI 48109-2200, USA. k2takeda@nodai.ac.jp
Kouji
K
Takeda
Tetsufumi
T
Ueda
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D010728:Phosphoenolpyruvate / Q000378:metabolism*; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*
D018698:Glutamic Acid; D000244:Adenosine Diphosphate; D010728:Phosphoenolpyruvate; D000255:Adenosine Triphosphate