Glutamat reaktion
Monosodium glutamate - Wikipedia
Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Caroline N. Authors Caroline N. Because of its sheer abundance throughout the central nervous system in parallel with its complicated role in several metabolic pathways, the function of glutamate as a neurotransmitter and its clinical significance has only recently been illuminated.
Glutamate is now acknowledged as the principal excitatory neurotransmitter in the central nervous system. Clinically, aberrant glutamatergic activity has been associated with addiction, psychosis, neurodegeneration, and glial cell death.
Glutamat-Dehydrogenase - SpringerLink
It has become a pharmacologic target in many areas of disease research. Glutamate is the principal excitatory neurotransmitter of the central nervous system and the most abundant neurotransmitter in the brain. It is stored within vesicles in axon terminals and released via exocytosis upon the influx of calcium cations.
The rate of its uptake from extracellular fluid largely regulates its concentration and actions in various compartments. Glutamate has clinical relevance in neurology and psychiatry, specifically regarding depression, substance use disorder, schizophrenia, neurodegenerative diseases, and other cognitive function and mood deficits. Although essential for normative functioning, excessive glutamate activity can precipitate excitotoxicity and neurodegeneration.
Agonist effects on NMDA, AMPA, kainate, and metabotropic receptors can explicate neurotoxic sequelae following cerebral ischemia, status epilepticus, and neurodegenerative diseases. Recent advances in neuroscience have revealed a genetic contribution to excitotoxic cell death diathesis and susceptibility. Of vital clinical importance are the implications of glutamatergic mediation on addiction and neurodegeneration.
Chronic drug use can induce glial cell injury, which leads to glutamate dysregulation and eventually alters cortico-striatal transmission to incentivize drug-seeking behaviors. Despite its potential as a pharmacological target for both substance use disorders and neurodegenerative states, the glutamate pathway has historically posed problems to researchers, including serious adverse effects like increased stroke risk.
As mentioned previously, glutamate is stored within vesicles in axon terminals and released via exocytosis upon the influx of calcium cations. Once in the cleft, glutamate binds to its reciprocal receptors precipitating either ion influx ionotropic receptors or signal transduction cascades metabotropic receptors , which then activate second messengers, ultimately regulating gene expression via neuroactive chemical release.
Structural basis for activation and filamentation of glutaminase
Glutamate is subsequently removed from the synaptic cleft via glutamate transporters, which are present on adjacent glial cells, as well as presynaptic terminals. Once transported into the glial cell, glutamate undergoes conversion to glutamine and is transported back into the nerve terminal where it is ultimately converted back into glutamate.
Glutamate connects the metabolic processes of neurons with those of astrocytes via the glutamate-glutamine cycle. After neuronal release, glutamate accumulates in astrocytes, converted to glutamine via glutamine synthetase an enzyme not found in neurons , phosphorylation, and ammonium NH4. Astrocytes can also synthesize glutamate de novo and release it via exocytosis due to another enzyme not found in neurons, pyruvate carboxylase, which generates the glutamate precursor alpha-ketoglutarate.
This synthesis seems to increase during brain activation, e. Neurons cannot synthesize glutamate or gamma-aminobutyric acid GABA , the primary inhibitory neurotransmitter, de novo from glucose.
Structural basis for activation and filamentation of glutaminase
Instead, they hydrolyze glutamate to glutamine via mitochondrial glutaminase at glutamatergic synapses or convert it via glutamate decarboxylase to GABA. Astrocytes, in turn, regenerate glutamate using glutamine and free ammonia, possibly released from neurons following their deamidation of glutamate at synapses, or synthesize glutamate de novo from glucose. The amount of de novo synthesis depends largely on the net loss of glutamate via oxidative reactions contributing to pyruvate recycling.
Glutamate is metabolized through the tricarboxylic acid cycle in both neurons and astrocytes, albeit to different extents. EAAT1 and 2 are primarily responsible for glutamate uptake in the brain, coupled with three sodium ions and one hydrogen ion entering the cell, and one potassium ion leaving, which maintains a 1,, inside-out concentration gradient. Glutamate has all the hallmarks of a conventional neurotransmitter, plus the added complexity of the neuronal-astrocytic interplay that contributes to its recycling and to regulating excitatory brain activity.
The excitatory neurotransmitter contributes to the consolidation of memories, which is the basis of long-term learning, via activation of NMDA, AMPA, and metabotropic receptors in the brain.