Lactate shuttle in glial cells (Homo sapiens)

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NeuronNeuron AstrocyteCapillary1-11Synaptic cleftHCO3-ATPNBC1pyruvateUDP-D-glucoseTCA cycleGlycolysisGLSH+SLC16A3CO2CAIVD-Glucose 1-phosphateglucoseNa+SLC16A7ADPlactateD-Glucose 6-phosphateSLC1A2Na+ K+ATPase OH-O2UDPGPPGlycogen synthesis and degradation CAIIGSSLC2A3glycogenK+PGM1NADPHHexokinaseglutaminePentose phosphate metabolismglutamateLDHAammoniaSLC16A1lactatepyruvateLDHBglucoseADPGlycolysisATPADPCO2CAIIH+HCO3-H+CO2glucoseSLC2A1CAIVNa+SLC2A1glutamateglutamateglutamineNa+HCO3-CAIIATPADPATPH+Na+K+K+ATPADPSLC2A1GLUR1GLUR2GLUR3GLUR4lactateH+


Description

Astrocyte-neuron lactate shuttle in Homo sapiens. The pathway shows the relation between neuronal activity and lactate production in astrocytes. These shuttles show how lactate can be broken down by lactate dehydrogenase into pyruvate which enters the TCA cycle in neurons.

In astrocytes, glucose undergoes glycolysis to be converted into pyruvate, which is then converted into lactate with the help of the LDHA enzyme. Lactate is then transported from astrocytes to neurons through the transporters SLC16A1, SLC16A3 and SLC16A7. There, lactate is converted to pyruvate with the help of the LDHB enzyme. Pyruvate formation is also increased by glucose entering the neuron through the SLC2A3 transporter, which undergoes glycolysis. Pyruvate enters the TCA cycle in the mitochondria of the neuron and ATP is produced. The ATP generated in the neurons is required for the glutamate neurotransmitters to be excreted from neurons into the synaptic cleft. Astrocytes take up the glutamate neurotransmitters through the transporter SLC1A2. For glutamate to be transported into the cell by the SLC1A2 transporter, Na+ must be cotransported into the cell. This increase in concentration of sodium ions inside the astrocyte is balanced by Na+/K+ ATPase which transports Na+ out of the cell while simultaneously transporting K+ into the cell. This transporter requires ATP to be activated, and the ADP produced can be regenerated into ATP during glycolysis in the astrocytes.

This lactate shuttle theory explains that lactate from astrocytes is preferentially used over glucose by neurons in a fully aerobic state and is the main supply of energy to our neurological system.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
134484view03:11, 22 July 2024EweitzOntology Term : 'neuron' added !
134483view03:10, 22 July 2024EweitzOntology Term : 'astrocyte' added !
134382view15:51, 21 July 2024EweitzModified description
129352view09:28, 27 March 2024MkutmonOntology Term : 'classic metabolic pathway' added !
125793view11:20, 10 March 2023DeSlConverted synaptic cleft DataNode to textLabel
125792view11:17, 10 March 2023DeSlRemoving 'Unknown' DataNodes, replaces with labels in graphical drawings
125568view22:54, 27 February 2023AlexanderPicoSe
125549view21:20, 26 February 2023AndraOntology Term : 'glial cell' added !
125526view17:06, 25 February 2023EgonwMade five pathways clickable
125268view13:51, 31 January 2023Ellaverheggensources
125267view13:38, 31 January 2023Ellaverheggensources
125228view13:09, 30 January 2023Ellaverheggendescription change
125225view11:40, 30 January 2023Cleopheebruchouupdate reaction
125202view13:07, 29 January 2023Cleopheebruchoudescription
125201view13:06, 29 January 2023CleopheebruchouDescription
125199view12:30, 29 January 2023Cleopheebruchouadded external references
125188view12:30, 27 January 2023CleopheebruchouChanging arrows
125173view14:08, 26 January 2023Cleopheebruchouupdated transporter names
125171view14:05, 26 January 2023Cleopheebruchouupdated reaction arrows
125132view16:56, 24 January 2023Celestecurreriaddition of ATPase
125131view16:40, 24 January 2023Celestecurrerichange arrows and receptors/transporters name
125129view16:36, 24 January 2023Ellaverheggencheck arrows and glutamine/glutamate uptake
125107view11:08, 23 January 2023Cleopheebruchoutransporter name
125100view00:39, 23 January 2023EweitzModified title
125082view13:50, 20 January 2023Ellaverheggenadded glutamate and glutamine uptake cycle
125072view13:45, 19 January 2023Ellaverheggentrial
125068view14:45, 18 January 2023CelestecurreriAdding colors
125064view11:21, 18 January 2023CelestecurreriAdding glut3
125052view12:25, 17 January 2023CleopheebruchouComplete pathway
125040view10:16, 17 January 2023CelestecurreriNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
CAIIProteinP00918 (Uniprot-TrEMBL)
CAIVProteinP22748 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
D-Glucose 1-phosphateMetaboliteCHEBI:16077 (ChEBI)
D-Glucose 6-phosphateMetaboliteCHEBI:4170 (ChEBI)
GLSProteino94925 (Uniprot-TrEMBL)
GLUR1Proteinp42261 (Uniprot-TrEMBL)
GLUR2Proteinp42262 (Uniprot-TrEMBL)
GLUR3Proteinp42263 (Uniprot-TrEMBL)
GLUR4Proteinp480458 (Uniprot-TrEMBL)
GSProteinp15104 (Uniprot-TrEMBL)
Glycogen synthesis

and degradation

PathwayWP500 (WikiPathways)
GlycolysisPathwayWP4629 (WikiPathways)
H+MetaboliteCHEBI:15378 (ChEBI)
HCO3-MetaboliteCHEBI:17544 (ChEBI)
HexokinaseProteinP19367 (Uniprot-TrEMBL)
K+MetaboliteCHEBI:29103 (ChEBI)
LDHAGeneProductENSG00000134333 (Ensembl)
LDHBGeneProductP07195 (Uniprot-TrEMBL)
NADPHMetaboliteHMDB00221 (HMDB)
NBC1ProteinQ9Y6R1 (Uniprot-TrEMBL)
Na+ K+ ATPase Proteinp50993 (Uniprot-TrEMBL)
Na+MetaboliteCHEBI:29101 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OH-MetaboliteCHEBI:16234 (ChEBI)
PGM1ProteinGene ID: 5236 (NCBI Protein)
Pentose phosphate metabolismPathwayWP134 (WikiPathways)
SLC16A1ProteinP53985 (Uniprot-TrEMBL)
SLC16A3ProteinO15427 (Uniprot-TrEMBL)
SLC16A7ProteinO60669 (Uniprot-TrEMBL)
SLC1A2ProteinP43004 (Uniprot-TrEMBL)
SLC2A1ProteinP11166 (Uniprot-TrEMBL)
SLC2A3ProteinP11169 (Uniprot-TrEMBL)
TCA cyclePathwayWP78 (WikiPathways)
UDP-D-glucoseMetaboliteCHEBI:18066 (ChEBI)
UDPGPPProteinO95848 (Uniprot-TrEMBL)
ammonia MetaboliteCHEBI:16134 (ChEBI)
glucoseMetaboliteCHEBI:17234 (ChEBI)
glutamateMetaboliteCHEBI:14321 (ChEBI)
glutamineMetaboliteCHEBI:28300 (ChEBI)
glycogenMetaboliteCHEBI:28087 (ChEBI)
lactateMetaboliteCHEBI:24996 (ChEBI)
pyruvateMetaboliteCHEBI:15361 (ChEBI)

Annotated Interactions

No annotated interactions
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