Glutamate is the major excitatory neurotransmitter in the central nervous system. During neurotransmission it is released from synaptic vesicles into the synaptic cleft and is sensed by post-synaptic glutamate receptors (GluAs) (1).
Excitatory amino acid transporters (EAATs) translocate extracellular glutamate into neighbouring astrocytes where it is converted to glutamine by glutamine synthetase (2, 3, 4).
The glutamine is shuttled back to neurons where it is processed to glutamate by glutaminases (GLS) (5). This postulated Glu/Gln cycle is a key mechanism for the homeostatic control of these amino acids.
In humans, three isoforms (GLS1, 2 and 3) have been described. GLS1 is highly expressed in brain and kidney whereas GLS2 is mainly expressed in cardiac and skeletal muscle. GLS3 shows a broader tissue distribution (5). The GLS1 precursor is processed to a 65 and 68 kDa chain.