Carnosine metabolism of glial cells (WP5313)

Homo sapiens

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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.

Authors

Jasmijn van Zaanen , Laetitia Flammang , Eric Weitz , Egon Willighagen , Isabel Wassink , and Kristina Hanspers

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

glial cell

Pathway Ontology

classic metabolic pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
ATP Metabolite chebi:30616
lactate Metabolite chebi:24996
Carnosine Metabolite chebi:15727
L-histidine Metabolite chebi:15971
BETA-ALANINE Metabolite chebi:16958
ADP Metabolite chebi:456216
K+ Metabolite chebi:29103
Na+ Metabolite chebi:29101
Carnosine Metabolite chebi:15727
glutamate Metabolite chebi:14321
L-carnosine Metabolite chebi:15727
BETA-ALANINE Metabolite chebi:16958
L-histidine Metabolite chebi:15971
Na+ Metabolite chebi:29101
glutamate Metabolite chebi:14321
ATP Metabolite chebi:30616
ADP Metabolite chebi:456216
Na+ Metabolite chebi:29101
K+ Metabolite chebi:29103
CARNS1 GeneProduct ensembl:ENSG00000172508
SLC6A6 GeneProduct ensembl:ENSG00000131389
SLC15A2 GeneProduct ensembl:ENSG00000163406
SLC15A2 GeneProduct ensembl:ENSG00000163406
SLC15A2 GeneProduct ensembl:ENSG00000163406
SLC15A4 GeneProduct ensembl:ENSG00000139370

References

  1. Β-alanine and l-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply. Usui T, Kubo Y, Akanuma SI, Hosoya KI. Exp Eye Res. 2013 Aug;113:135–42. PubMed Europe PMC Scholia
  2. Physiology and pathophysiology of carnosine. Boldyrev AA, Aldini G, Derave W. Physiol Rev. 2013 Oct;93(4):1803–45. PubMed Europe PMC Scholia
  3. Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery. Ouyang L, Tian Y, Bao Y, Xu H, Cheng J, Wang B, et al. Brain Res Bull. 2016 Jun;124:76–84. PubMed Europe PMC Scholia
  4. Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders. Caruso G, Caraci F, Jolivet RB. Prog Neurobiol. 2019 Apr;175:35–53. PubMed Europe PMC Scholia
  5. The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence. Schön M, Mousa A, Berk M, Chia WL, Ukropec J, Majid A, et al. Nutrients. 2019 May 28;11(6):1196. PubMed Europe PMC Scholia
  6. Transport of Amino Acids Across the Blood-Brain Barrier. Zaragozá R. Front Physiol. 2020 Sep 23;11:973. PubMed Europe PMC Scholia
  7. Carnosine, Small but Mighty-Prospect of Use as Functional Ingredient for Functional Food Formulation. Jukić I, Kolobarić N, Stupin A, Matić A, Kozina N, Mihaljević Z, et al. Antioxidants (Basel). 2021 Jun 28;10(7):1037. PubMed Europe PMC Scholia
  8. Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases. Solana-Manrique C, Sanz FJ, Martínez-Carrión G, Paricio N. Antioxidants (Basel). 2022 Apr 26;11(5):848. PubMed Europe PMC Scholia