Carnosine metabolism of glial cells (Homo sapiens)

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1, 5, 7Macrophages & Microglia LiverAstrocyteIntestinesOligodendrocyteUracil and Thymine degradation Blood Brain Barrier3361Lactate ShuttleK+ATPL-histidineADPSLC6A6CarnosineGlycolysislactateATPaseCarnosine degradation CN1SLC7A5Na+L-carnosineglutamateCARNS1SLC1A2/GLT-1BETA-ALANINECarnosineBETA-ALANINE2418SLC15A2SLC15A2SLC15A2SLC15A4L-histidineNa+glutamateATPADPCN2Na+K+


Description

This pathway shows the synthesis and degradation of Carnosine as well as the distribution within glial cells in the brain.

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.

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Quality Tags

Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. Zaragozá R; ''Transport of Amino Acids Across the Blood-Brain Barrier.''; Front Physiol, 2020 PubMed Europe PMC Scholia
  5. 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
  6. 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
  7. Boldyrev AA, Aldini G, Derave W; ''Physiology and pathophysiology of carnosine.''; Physiol Rev, 2013 PubMed Europe PMC Scholia
  8. 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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CompareRevisionActionTimeUserComment
127653view23:23, 13 November 2023Khanspersremoved unecessary WPID references
125782view09:46, 10 March 2023IsabelWassinkOntology Term : 'glial cell' added !
125780view09:45, 10 March 2023IsabelWassinkOntology Term : 'classic metabolic pathway' added !
125592view06:42, 3 March 2023EgonwNot a mim-conversion
125591view06:33, 3 March 2023EgonwRemoved two template comments
125590view06:24, 3 March 2023EgonwRemoved two incorrect identifiers
125524view16:47, 25 February 2023EgonwMade two pathways clickable
125257view09:39, 31 January 2023TichaLink to lactate shuttle
125256view09:32, 31 January 2023Jasmijnvanzaanenmoving of metabolites
125255view09:26, 31 January 2023Jasmijnvanzaanenadding links to pathways
125183view12:00, 27 January 2023Jasmijnvanzaanenadding metabolites
125182view11:54, 27 January 2023Jasmijnvanzaanenadding description of pathway
125127view14:06, 24 January 2023Jasmijnvanzaanenmoving transporters and adding literature
125108view11:17, 23 January 2023Tichalocation of transporter
125102view00:40, 23 January 2023EweitzModified title
125083view13:50, 20 January 2023TichaUpdate on some Genes
125076view10:30, 20 January 2023TichaColor and CNDP1
125067view12:14, 18 January 2023TichaAdd transporters in BBB for Amino acids to pass
125066view11:56, 18 January 2023Jasmijnvanzaanenadding arrows
125065view11:47, 18 January 2023Jasmijnvanzaanenadding connection to lactate shuttle
125059view19:03, 17 January 2023Tichaoutline changes
125058view18:32, 17 January 2023Tichaaddition of carnosinases, blood brain barrier
125055view15:26, 17 January 2023Tichachanges and additions
125054view14:55, 17 January 2023Jasmijnvanzaanenmoving transporters
125039view10:13, 17 January 2023Jasmijnvanzaanenadding literature references
125029view09:20, 16 January 2023Jasmijnvanzaanenadding identifiers to each node.
125028view09:13, 16 January 2023JasmijnvanzaanenNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
ATPaseProtein
BETA-ALANINEMetaboliteCHEBI:16958 (ChEBI)
CARNS1GeneProductENSG00000172508 (Ensembl)
CN1GeneProduct
CN2GeneProduct
Carnosine degradation Pathway
CarnosineMetaboliteCHEBI:15727 (ChEBI)
GlycolysisPathwayWP4629 (WikiPathways) https://www.wikipathways.org/index.php/Pathway:WP4629
K+MetaboliteCHEBI:29103 (ChEBI)
L-carnosineMetaboliteCHEBI:15727 (ChEBI)
L-histidineMetaboliteCHEBI:15971 (ChEBI)
Lactate ShuttlePathwayWP5314 (WikiPathways) https://www.wikipathways.org/index.php/Pathway:WP5314
Na+MetaboliteCHEBI:29101 (ChEBI)
SLC15A2GeneProductENSG00000163406 (Ensembl)
SLC15A4GeneProductENSG00000139370 (Ensembl)
SLC1A2/GLT-1GeneProductGLT-1 is the name used in mouse and rat studies, and SLC1A2 in humans, however neither can be found in the database.
SLC6A6GeneProductENSG00000131389 (Ensembl)
SLC7A5GeneProduct
glutamateMetaboliteCHEBI:14321 (ChEBI)
lactateMetaboliteCHEBI:24996 (ChEBI)

Annotated Interactions

No annotated interactions

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