RT Journal Article
SR Electronic
T1 Neuronal Pyruvate Carboxylation Supports Formation of Transmitter Glutamate
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1342
OP 1347
DO 10.1523/JNEUROSCI.20-04-01342.2000
VO 20
IS 4
A1 Bjørnar Hassel
A1 Anders Bråthe
YR 2000
UL http://www.jneurosci.org/content/20/4/1342.abstract
AB Release of transmitter glutamate implies a drain of α-ketoglutarate from neurons, because glutamate, which is formed from α-ketoglutarate, is taken up by astrocytes. It is generally believed that this drain is compensated by uptake of glutamine from astrocytes, because neurons are considered incapable of de novosynthesis of tricarboxylic acid cycle intermediates, which requires pyruvate carboxylation. Here we show that cultured cerebellar granule neurons form releasable [14C]glutamate from H14CO3− and [1-14C]pyruvate via pyruvate carboxylation, probably mediated by malic enzyme. The activity of pyruvate carboxylation was calculated to be approximately one-third of the pyruvate dehydrogenase activity in neurons. Furthermore, intrastriatal injection of NaH14CO3 or [1-14C]pyruvate labeled glutamate better than glutamine, showing that pyruvate carboxylation occurs in neurons in vivo. This means that neurons themselves to a large extent may support their release of glutamate, and thus entails a revision of the current view of glial–neuronal interactions and the importance of the glutamine cycle.