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Journal of Neurochemistry Aug 2006Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA)... (Review)
Review
Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA-glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA-glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi-directional transfer of not only carbon units but also nitrogen units.
Topics: Ammonia; Animals; Biological Transport; Glutamic Acid; Glutamine; Homeostasis; Humans; gamma-Aminobutyric Acid
PubMed: 16787421
DOI: 10.1111/j.1471-4159.2006.03913.x -
Journal of Pharmacological Sciences Nov 2020Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamate transmission efficiency depends on the correct functionality and expression... (Review)
Review
Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamate transmission efficiency depends on the correct functionality and expression of a plethora of receptors and transporters, located both on neurons and glial cells. Of note, glutamate reuptake by dedicated transporters prevents its accumulation at the synapse as well as non-physiological spillover. Indeed, extracellular glutamate increase causes aberrant synaptic signaling leading to neuronal excitotoxicity and death. Moreover, extrasynaptic glutamate diffusion is strongly associated with glia reaction and neuroinflammation. Glutamate-induced excitotoxicity is mainly linked to an impaired ability of glial cells to reuptake and respond to glutamate, then this is considered a common hallmark in many neurodegenerative diseases, including Parkinson's disease (PD). In this review, we discuss the function of astrocytes and microglia in glutamate homeostasis, focusing on how glial dysfunction causes glutamate-induced excitotoxicity leading to neurodegeneration in PD.
Topics: Amino Acid Transport System X-AG; Glutamic Acid; Homeostasis; Humans; Inflammation; Neuroglia; Neurotransmitter Agents; Parkinson Disease; Receptors, Glutamate
PubMed: 32807662
DOI: 10.1016/j.jphs.2020.07.011 -
Scientific Reports Jul 2021Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin...
Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.
Topics: Animals; Apoptosis; Cell Line; Cell Proliferation; Computer Simulation; Drug Development; Fibroblasts; Glutamic Acid; Hair; Hair Follicle; Humans; Keratinocytes; Male; Mice; Protein Interaction Mapping; Regeneration; Signal Transduction; Skin; Skin Physiological Phenomena
PubMed: 34326383
DOI: 10.1038/s41598-021-94816-y -
Biological Psychiatry Jan 2020Opioid administration in preclinical models induces long-lasting adaptations in reward and habit circuitry. The latest research demonstrates that in the nucleus... (Review)
Review
Opioid administration in preclinical models induces long-lasting adaptations in reward and habit circuitry. The latest research demonstrates that in the nucleus accumbens, opioid-induced excitatory synaptic plasticity involves presynaptic and postsynaptic elements as well as adjacent astroglial processes and the perisynaptic extracellular matrix. We outline opioid-induced modifications within each component of the tetrapartite synapse and provide a neurobiological perspective on how these adaptations converge to produce addiction-related behaviors in rodent models. By incorporating changes observed at each of the excitatory synaptic compartments into a unified framework of opioid-induced glutamate dysregulation, we highlight new avenues for restoring synaptic homeostasis that might limit opioid craving and relapse vulnerability.
Topics: Analgesics, Opioid; Glutamic Acid; Neuronal Plasticity; Nucleus Accumbens; Synapses
PubMed: 31378302
DOI: 10.1016/j.biopsych.2019.05.025 -
Annals of Nutrition & Metabolism 2018Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group... (Review)
Review
BACKGROUND
Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight (bw)/day.
SUMMARY
This ADI is below the normal dietary intake, while even intake of free glutamate by breast-fed babies can be above this ADI. In addition, the pre-natal developmental toxicity study selected by EFSA, has never been used by regulatory authorities worldwide for the safety assessment of glutamate despite it being available for nearly 40 years. Also, the EFSA ignored that toxicokinetic data provide support for eliminating the use of an uncertainty factor for interspecies differences in kinetics. Key Messages: A 3-generation reproductive toxicity study in mice that includes extensive brain histopathology, provides a better point of departure showing no effects up to the highest dose tested of 6,000 mg/kg bw/day. Furthermore, kinetic data support use of a compound-specific uncertainty factor of 25 instead of 100. Thus, an ADI of at least 240 mg/kg bw/day would be indicated. In fact, there is no compelling evidence to indicate that the previous ADI of "not specified" warrants any change.
Topics: Animals; Food Additives; Glutamic Acid; Humans; Mice; No-Observed-Adverse-Effect Level; Rats; Risk Assessment; Toxicokinetics
PubMed: 30508819
DOI: 10.1159/000494783 -
Journal of Oleo Science Aug 2022Hydrogels formed by low-molecular-weight gelators have reversible sol-gel transition and responsiveness to various stimuli, and are used in cosmetics and drug...
Hydrogels formed by low-molecular-weight gelators have reversible sol-gel transition and responsiveness to various stimuli, and are used in cosmetics and drug applications. It is challenging to obtain hydrogels using novel gelators because subtle differences in their molecular architecture affect gelation. Organogelators (which form organogels) are insoluble in water, and their use as hydrogelators has not previously been considered. However, a surfactant-mediated gelation method was reported in which organogelators were solubilized in water by surfactants to form hydrogels using 12-hydroxyoctadecanoic acid. To investigate whether this method can be applied with other organogelators, the formation of hydrogel using a glutamic-acid-based organogelator was studied here. Hydrogels were formed by solubilizing 1:1 mixtures of glutamate-based organogelators, N-lauroyl-L-glutamic acid dibuthylamide, and N-2-ethylhexanoyl-L-glutamic acid dibutylamide in aqueous micellar solutions of anionic surfactant (sodium lauroyl glutamate) and cationic surfactant (cetyltrimethylammonium chloride). The minimum gelation concentration of the hydrogel was ~0.2-0.6 wt%. By changing the molar fraction of cetyltrimethylammonium chloride in the mixed surfactant, either spherical or wormlike micelles were formed. The hydrogel with wormlike micelles had a higher sol-gel transition temperature than that with spherical micelles and formed fine self-assembled fibrillar networks. Additionally, the hydrogel with the spherical micelles was elastic, whereas that with wormlike micelles was viscoelastic, suggesting that networks of the organogelators and wormlike micelles coexisted in the hydrogel from the wormlike micellar solution. Moreover, the hydrogel suppressed the reduction in the storage modulus at higher temperatures compared with the micellar aqueous solution, indicating that the elastic properties of the organogelator networks were maintained at high temperatures. The gel fibers of the hydrogel partially formed a loosely aggregated structure as the temperature increased, the fibers bundled via hydrophobic interactions, and new cross-linking points formed spontaneously. This phenomenon corresponded with an inflection point in the temperature-dependent storage modulus of the hydrogel.
Topics: Cetrimonium; Excipients; Glutamic Acid; Hydrogels; Micelles; Pulmonary Surfactants; Surface-Active Agents; Water
PubMed: 35793975
DOI: 10.5650/jos.ess22080 -
Annals of Nutrition & Metabolism 2018Glutamate (Glu), either as one of the amino acids of protein or in free form, constitutes up to 8-10% of amino acid content in the human diet, with an intake of about... (Review)
Review
Glutamate (Glu), either as one of the amino acids of protein or in free form, constitutes up to 8-10% of amino acid content in the human diet, with an intake of about 10-20 g/day in adults. In the intestine, postprandial luminal Glu concentrations can be of the order of mM and result in a high intra-mucosal Glu concentration. Glu absorbed from the intestinal lumen is for a large part metabolized by enterocytes in various pathways, including the production of energy to support intestinal motility and functions. Glu is the most important fuel for intestinal tissue, it is involved in gut protein metabolism and is the precursor of different important molecules produced within the intestinal mucosa (2-oxoglutarate, L-alanine, ornithine, arginine, proline, glutathione, γ-aminobutyric acid [GABA]). Studies in adult humans, pigs, piglets or preterm infants indicate that a large proportion of Glu is metabolized in the intestine, and that for the usual range of Glu dietary intake (bound Glu and free Glu including added Glu as a food additive in normal amounts up to 1 g/day), circulating Glu is tightly maintained at rather low concentrations. Systemic blood levels of Glu transiently rise when high doses monosodium glutamate (> 10-12 g), higher than normal human dietary consumption, are ingested and normalize within 2 h after the offset of consumption. Glu is also involved in oral and post oral nutrient chemosensing that involves gustatory nerves and both humoral and neural (vagal) gut-brain pathways with an impact on gut function and feeding behavior. Glu functions as a signaling molecule in the enteric nervous system and modulates neuroendocrine reflexes in the gastrointestinal tract. The oral taste sensation of Glu involves its binding to the oral umami taste receptors that triggers the cephalic phase response of digestion to prepare for food digestion. Glu is sensed again in the gut, inducing a visceral sensation that enhances additional gut digestive processes through the visceral sense (vago-vagal reflex).
Topics: Animals; Diet; Glutamic Acid; Humans; Intestines; Signal Transduction; Taste
PubMed: 30508814
DOI: 10.1159/000494777 -
Clinical & Experimental Optometry May 2013Advances in basic retinal anatomy, genetics, biochemical pathways and neurochemistry have not only provided a better understanding of retinal function but have also... (Review)
Review
Advances in basic retinal anatomy, genetics, biochemical pathways and neurochemistry have not only provided a better understanding of retinal function but have also allowed us to link basic science to retinal disease. The link with disease allowed measures to be developed that now provide an opportunity to intervene and slow down or even restore sight in previously 'untreatable' retinal diseases. One of the critical advances has been the understanding of the retinal amino acid neurotransmitters, related amino acids, their metabolites and functional receptors. This review provides an overview of amino acid localisation in the retina and examples of how retinal anatomy and amino acid neurochemistry directly links to understanding retinal disease. Also, the implications of retinal remodelling involving amino acid (glutamate) receptors are outlined in this review and insights are presented on how understanding of detrimental and beneficial retinal remodelling will provide better outcomes for patients using strategies for the preservation or restoration of vision. An internet-based database of retinal images of amino acid labelling patterns and other amino acid-related images in health and disease is located at http://www.aminoacidimmunoreactivity.com.
Topics: Amino Acids; Glutamic Acid; Glycine; Humans; Recovery of Function; Retina; Retinal Diseases; Synaptic Transmission; Taurine; gamma-Aminobutyric Acid
PubMed: 23464379
DOI: 10.1111/cxo.12015 -
Journal of Neural Transmission (Vienna,... Aug 2014Glutamate, a nonessential amino acid, is a major bioenergetic substrate for proliferating normal and neoplastic cells on one hand and an excitatory neurotransmitter that... (Review)
Review
Glutamate, a nonessential amino acid, is a major bioenergetic substrate for proliferating normal and neoplastic cells on one hand and an excitatory neurotransmitter that is actively involved in biosynthetic, bioenergetic, metabolic, and oncogenic signaling pathways on the other. It exerts its action through a family of receptors consisting of metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated previously in a broad spectrum of acute and chronic neurodegenerative diseases. In this review, we discuss existing data on the role of glutamate as a growth factor for neoplastic cells, the expression of glutamate receptors in various types of benign and malignant neoplasms, and the potential roles that GluRs play in cancer development and progression along with their clinical significance. We conclude that glutamate-related receptors and their signaling pathways may provide novel therapeutic opportunities for a variety of malignant human diseases.
Topics: Animals; Glutamic Acid; Humans; Neoplasms; Receptors, Glutamate
PubMed: 24610491
DOI: 10.1007/s00702-014-1182-6 -
Skin Research and Technology : Official... Jan 2024Excessive inflammation may cause tissue damage and disrupt the function of the skin barrier. Hyaluronic acid (HA), an endogenous component, was found to regulate...
BACKGROUND
Excessive inflammation may cause tissue damage and disrupt the function of the skin barrier. Hyaluronic acid (HA), an endogenous component, was found to regulate multiple inflammatory factors for skin health. This work aims to further enhance its efficacy by grafting amino acid onto its molecule.
METHODS
Glutamic acid (Glu) was selected as the ligand to react with low-molecular-weight HA. Fibroblast tests and a 3D skin model were used to investigate the anti-inflammation efficacy of HA-Glu.
RESULTS
For IL-1α, IL-6 and TNF-α, the grafted compound presents stronger inhibition ability versus native HA. Moreover, HA-Glu could promote the repair of damaged skin by improving the compactness of the stratum corneum and increasing the thickness of the living cell layer.
CONCLUSION
The application of HA-Glu compound in skin care formulas would be effective to alleviate inflammation-induced skin symptoms and skin aging.
Topics: Humans; Hyaluronic Acid; Glutamic Acid; Skin; Inflammation; Fibroblasts
PubMed: 38174788
DOI: 10.1111/srt.13548