Lactate shuttle in glial cells (WP5314)

Homo sapiens

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.

Authors

Celestecurreri , Cléophée Bruchou , Ellaverheggen , Eric Weitz , Egon Willighagen , Andra Waagmeester , Alex Pico , Denise Slenter , and Martina Summer-Kutmon

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

glial cell neuron astrocyte

Pathway Ontology

classic metabolic pathway

Participants

Label Type Compact URI Comment
HCO3- Metabolite chebi:17544
ATP Metabolite chebi:30616
pyruvate Metabolite chebi:15361
UDP-D-glucose Metabolite chebi:18066
H+ Metabolite chebi:15378
CO2 Metabolite chebi:16526
D-Glucose 1-phosphate Metabolite chebi:16077
glucose Metabolite chebi:17234
Na+ Metabolite chebi:29101
ADP Metabolite chebi:456216
lactate Metabolite chebi:24996
D-Glucose 6-phosphate Metabolite chebi:4170
OH- Metabolite chebi:16234
O2 Metabolite chebi:15379
glycogen Metabolite chebi:28087
K+ Metabolite chebi:29103
NADPH Metabolite hmdb:HMDB00221
glutamine Metabolite chebi:28300
glutamate Metabolite chebi:14321
ammonia Metabolite chebi:16134
LDHA GeneProduct ensembl:ENSG00000134333
LDHB GeneProduct uniprot:P07195
NBC1 Protein uniprot:Q9Y6R1
GLS Protein uniprot:o94925
SLC16A3 Protein uniprot:O15427
CAIV Protein uniprot:P22748
SLC16A7 Protein uniprot:O60669
SLC1A2 Protein uniprot:P43004
Na+ K+ATPase Protein uniprot:p50993
UDPGPP Protein uniprot:O95848
CAII Protein uniprot:P00918
GS Protein uniprot:p15104
SLC2A3 Protein uniprot:P11169
PGM1 Protein ncbiprotein:Gene ID: 5236
Hexokinase Protein uniprot:P19367
SLC16A1 Protein uniprot:P53985
SLC2A1 Protein uniprot:P11166
GLUR1 Protein uniprot:p42261
GLUR2 Protein uniprot:p42262
GLUR3 Protein uniprot:p42263
GLUR4 Protein uniprot:p480458

References