Aerobic Glycolysis in the Brain: Warburg and Crabtree Contra Pasteur
Neurochem Res. 2020-01-24; :
DOI: 10.1007/s11064-020-02964-w
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Information processing is onerous. Curiously, active brain tissue does not fully
oxidize glucose and instead generates a local surplus of lactate, a phenomenon
termed aerobic glycolysis. Why engage in inefficient ATP production by glycolysis
when energy demand is highest and oxygen is plentiful? Aerobic glycolysis is
associated to classic biochemical effects known by the names of Pasteur, Warburg
and Crabtree. Here we discuss these three interdependent phenomena in brain
cells, in light of high-resolution data of neuronal and astrocytic metabolism in
culture, tissue slices and in vivo, acquired with genetically-encoded fluorescent
sensors. These sensors are synthetic proteins that can be targeted to specific
cell types and subcellular compartments, which change their fluorescence in
response to variations in metabolite concentration. A major site of acute aerobic
glycolysis is the astrocyte. In this cell, a Crabtree effect triggered by K+
coincides with a Warburg effect mediated by NO, superimposed on a slower
longer-lasting Warburg effect caused by glutamate and possibly by NH4+. The
compounded outcome is that more fuel (lactate) and more oxygen are made available
to neurons, on demand. Meanwhile neurons consume both glucose and lactate,
maintaining a strict balance between glycolysis and respiration, commanded by the
Na+ pump. We conclude that activity-dependent Warburg and Crabtree effects in
brain tissue, and the resulting aerobic glycolysis, do not reflect inefficient
energy generation but the marshalling of astrocytes for the purpose of neuronal
ATP generation. It remains to be seen whether neurons contribute to aerobic
glycolysis under physiological conditions.