Glutamate-glutamine cycle
Encyclopedia
In biochemistry
, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter
glutamate is maintained in the central nervous system
.
Initially, glial cell
s release glutamine
, which is then taken up into presynaptic terminals and metabolized into glutamate by glutaminase
(a mitochondrial enzyme
). Glutamate can also be produced by transamination
of 2-oxoglutarate, an intermediate in the Citric acid cycle
.
The glutamate that is synthesized in the presynaptic terminal is packaged into synaptic vesicle
s by the transporter VGLUT. Once the vesicle is released, glutamate is removed from the synaptic cleft by excitatory amino acid transporters (EAATs), of which there are five types. Glutamate taken up by glial cells is then converted into glutamine by glutamine synthetase
, and transported out of the cells into the nerve terminal. This allows synaptic terminals and glial cells to work together in order to maintain a proper supply of glutamate.
At GABAergic synapses, the cycle is called the GABA-glutamine cycle. Here the glutamine taken up by neurons is converted to glutamate, which is then metabolized into GABA by glutamate decarboxylase
. Upon release, GABA is taken up by glial cells via GABA transporters, metabolized into succinate, then in a series of steps to alpha-ketoglutarate and then back to glutamine via glutamate.
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
glutamate is maintained in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
Initially, glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s release glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
, which is then taken up into presynaptic terminals and metabolized into glutamate by glutaminase
Glutaminase
Glutaminase is an amidohydrolase enzyme which generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Importantly, glutaminase is found in glial cells.Glutaminase catalyzes the following reaction:Glutamine + H2O → Glutamate + NH3...
(a mitochondrial enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
). Glutamate can also be produced by transamination
Transamination
There are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...
of 2-oxoglutarate, an intermediate in the Citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
.
The glutamate that is synthesized in the presynaptic terminal is packaged into synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s by the transporter VGLUT. Once the vesicle is released, glutamate is removed from the synaptic cleft by excitatory amino acid transporters (EAATs), of which there are five types. Glutamate taken up by glial cells is then converted into glutamine by glutamine synthetase
Glutamine synthetase
Glutamine synthetase is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine:Glutamate + ATP + NH3 → Glutamine + ADP + phosphate...
, and transported out of the cells into the nerve terminal. This allows synaptic terminals and glial cells to work together in order to maintain a proper supply of glutamate.
At GABAergic synapses, the cycle is called the GABA-glutamine cycle. Here the glutamine taken up by neurons is converted to glutamate, which is then metabolized into GABA by glutamate decarboxylase
Glutamate decarboxylase
Glutamate decarboxylase or glutamic acid decarboxylase is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor. The reaction proceeds as follows:...
. Upon release, GABA is taken up by glial cells via GABA transporters, metabolized into succinate, then in a series of steps to alpha-ketoglutarate and then back to glutamine via glutamate.