Carnosine metabolism of glial cells (Homo sapiens)
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Description
The synthesis pathway starts at two different locations, with beta-alanine being transported from the liver and l-histidine being transported from the intestines, since it needs to be ingested. As can be seen, various transports bring these two amino acids across the blood brain barrier and into the oligodendrocyte where the actual synthesis of carnosine happens by CARNS1. The degradation of carnosine also occurs within the oligodendrocyte by CN1 and CN2. The oligdendrocytes are the only glial cells in the brain which produce carnosine, but all of them use it, so distribution to other glial cells is necessary. The transport to microglia is done by SLC14A2 and 4, while transport to astrocytes only requires SLC14A2.
Carnosine also has an impact on the glutamate transporter of the astrocyte, which is SLC1A2, also known as GLT-1. Carnosine stimulates the transporter, which brings more glutamate and sodium into the cell. The sodium concentration within the cell will be increased, leading to a higher activity of the ATPase. This generates more ADP, which can be used within glycolysis. This then builds a connected to the lactate shuttle which occurs between the astrocyte and neurons, in which the astrocyte produces lactate from pyruvate to give the neurons additional energy support.Quality Tags
Ontology Terms
Bibliography
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- Caruso G, Caraci F, Jolivet RB; ''Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders.''; Prog Neurobiol, 2019 PubMed Europe PMC Scholia
- Usui T, Kubo Y, Akanuma S, Hosoya K; ''Β-alanine and l-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply.''; Exp Eye Res, 2013 PubMed Europe PMC Scholia
- Jukić I, Kolobarić N, Stupin A, Matić A, Kozina N, Mihaljević Z, Mihalj M, Šušnjara P, Stupin M, Ćurić ŽB, Selthofer-Relatić K, Kibel A, Lukinac A, Kolar L, Kralik G, Kralik Z, Széchenyi A, Jozanović M, Galović O, Medvidović-Kosanović M, Drenjančević I; ''Carnosine, Small but Mighty-Prospect of Use as Functional Ingredient for Functional Food Formulation.''; Antioxidants (Basel), 2021 PubMed Europe PMC Scholia
- Zaragozá R; ''Transport of Amino Acids Across the Blood-Brain Barrier.''; Front Physiol, 2020 PubMed Europe PMC Scholia
- Solana-Manrique C, Sanz FJ, Martínez-Carrión G, Paricio N; ''Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases.''; Antioxidants (Basel), 2022 PubMed Europe PMC Scholia
- Schön M, Mousa A, Berk M, Chia WL, Ukropec J, Majid A, Ukropcová B, de Courten B; ''The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.''; Nutrients, 2019 PubMed Europe PMC Scholia
- Boldyrev AA, Aldini G, Derave W; ''Physiology and pathophysiology of carnosine.''; Physiol Rev, 2013 PubMed Europe PMC Scholia
- Ouyang L, Tian Y, Bao Y, Xu H, Cheng J, Wang B, Shen Y, Chen Z, Lyu J; ''Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery.''; Brain Res Bull, 2016 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ADP | Metabolite | CHEBI:456216 (ChEBI) | |
ATP | Metabolite | CHEBI:30616 (ChEBI) | |
ATPase | Protein | ||
BETA-ALANINE | Metabolite | CHEBI:16958 (ChEBI) | |
CARNS1 | GeneProduct | ENSG00000172508 (Ensembl) | |
CN1 | GeneProduct | ||
CN2 | GeneProduct | ||
Carnosine degradation | Pathway | ||
Carnosine | Metabolite | CHEBI:15727 (ChEBI) | |
Glycolysis | Pathway | WP4629 (WikiPathways) | https://www.wikipathways.org/index.php/Pathway:WP4629 |
K+ | Metabolite | CHEBI:29103 (ChEBI) | |
L-carnosine | Metabolite | CHEBI:15727 (ChEBI) | |
L-histidine | Metabolite | CHEBI:15971 (ChEBI) | |
Lactate Shuttle | Pathway | WP5314 (WikiPathways) | https://www.wikipathways.org/index.php/Pathway:WP5314 |
Na+ | Metabolite | CHEBI:29101 (ChEBI) | |
SLC15A2 | GeneProduct | ENSG00000163406 (Ensembl) | |
SLC15A4 | GeneProduct | ENSG00000139370 (Ensembl) | |
SLC1A2/GLT-1 | GeneProduct | GLT-1 is the name used in mouse and rat studies, and SLC1A2 in humans, however neither can be found in the database. | |
SLC6A6 | GeneProduct | ENSG00000131389 (Ensembl) | |
SLC7A5 | GeneProduct | ||
glutamate | Metabolite | CHEBI:14321 (ChEBI) | |
lactate | Metabolite | CHEBI:24996 (ChEBI) |
Annotated Interactions
No annotated interactions