Cori cycle (WP1946)

The Cori cycle (also known as the Lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate. Muscular activity requires ATP, which is provided by the breakdown of glycogen in the skeletal muscles. The breakdown of glycogen, a process known as glycogenolysis, releases glucose in the form of glucose-1-phosphate (G-1-P). The G-1-P is converted to G-6-P by the enzyme phosphoglucomutase. G-6-P is readily fed into glycolysis, (or can go into the pentose phosphate pathway if G-6-P concentration is high) a process that provides ATP to the muscle cells as an energy source. During muscular activity, the store of ATP needs to be constantly replenished. When the supply of oxygen is sufficient, this energy comes from feeding pyruvate, one product of glycolysis, into the Krebs cycle. When oxygen supply is insufficient, typically during intense muscular activity, energy must be released through anaerobic metabolism. Lactic acid fermentation converts pyruvate to lactate by lactate dehydrogenase. Most importantly, fermentation regenerates NAD+, maintaining the NAD+ concentration so that additional glycolysis reactions can occur. The fermentation step oxidizes the NADH produced by glycolysis back to NAD+, transferring two electrons from NADH to reduce pyruvate into lactate. Instead of accumulating inside the muscle cells, lactate produced by anaerobic fermentation is taken up by the liver. This initiates the other half of the Cori cycle. In the liver, gluconeogenesis occurs. From an intuitive perspective, gluconeogenesis reverses both glycolysis and fermentation by converting lactate first into pyruvate, and finally back to glucose. The glucose is then supplied to the muscles through the bloodstream; it is ready to be fed into further glycolysis reactions. If muscle activity has stopped, the glucose is used to replenish the supplies of glycogen through glycogenesis. Overall, the glycolysis part of the cycle produces 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis part. Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules indicates that the Cori cycle shifts the metabolic burden from the muscles to the liver. Source: [https://en.wikipedia.org/wiki/Cori_cycle Wikipedia] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1946 CPTAC Assay Portal]
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Authors

Ersaxton, AlexanderPico, MaintBot, Khanspers, Mkutmon, MartijnVanIersel, Egonw, Zari, DeSl, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: energy metabolic pathway

Participants

Label Type Compact Identifier
6P gluconate Metabolite chebi:48928
1,3-biphosphoglycerate Metabolite chebi:89363
SLC2A4 GeneProduct ensembl:ENSG00000181856
G6P Metabolite hmdb:HMDB0001401
Isomerase GeneProduct eccode:5.3.1.6
NAD+ Metabolite chebi:15846
Glycogenolysis Pathway None
GPI GeneProduct ensembl:ENSG00000105220
Alanine Metabolite chebi:16449
Glycogenesis Pathway None
3-Phosphoglycerate Metabolite chebi:17050
D-Fructose-6-phosphate Metabolite chebi:15946
GPT GeneProduct ensembl:ENSG00000167701
Xylulose Metabolite chebi:27353
ribulose Metabolite chebi:28721
Xylulose Metabolite chebi:27353
Glycogen Metabolite chebi:28087
Pyruvate Kinase GeneProduct eccode:2.7.1.40
Pyruvate Metabolite chebi:15361
Fructose 6P Metabolite hmdb:HMDB0000124
Hexokinase GeneProduct ncbigene:3098
Fructose 1,6-bisphosphate Metabolite hmdb:HMDB0001058
Gluconolactonase GeneProduct eccode:3.1.1.17
DHAP Metabolite chebi:16108
SLC2A1 GeneProduct ensembl:ENSG00000117394
2-phosphoglycerate(3-) Metabolite wikidata:Q27160201
Transketolase Protein eccode:2.2.1.1
Glycolosis Pathway None
G6P Metabolite hmdb:HMDB0001401
6P Gluconate DH Protein ensembl:ENSG00000160211
NADH Metabolite chebi:16908
Pyruvate Metabolite chebi:15361
PGAM1 GeneProduct ensembl:ENSG00000171314
LDHA GeneProduct ensembl:ENSG00000134333
G3P Metabolite chebi:17138
G3P Metabolite hmdb:HMDB0001112
Lactate Metabolite chebi:24996
Sedoheptulose Metabolite chebi:16802
Insulin GeneProduct ncbigene:3630
Phosphoenol Pyruvate Metabolite chebi:58702
G3P Metabolite chebi:17138
Gluconeogenesis Pathway None
Glucose Metabolite hmdb:HMDB0000122
SLC2A2 GeneProduct ensembl:ENSG00000163581
H2O Metabolite chebi:15377
6-Phosphogluconolactone Metabolite chemspider:388559
Ribose Metabolite chebi:33942
Epimerase Protein eccode:5.1.3.22
GAPDH GeneProduct ensembl:ENSG00000111640
SLC2A4 GeneProduct ensembl:ENSG00000181856
PFKP GeneProduct ensembl:ENSG00000067057
ALDOA Protein uniprot:P04075
PGK1 GeneProduct ensembl:ENSG00000102144
Enolase GeneProduct eccode:4.2.1.11
Hexokinase GeneProduct ncbigene:3098
G6P Metabolite hmdb:HMDB0001401
Pyruvate Metabolite chebi:15361
GPT GeneProduct ensembl:ENSG00000167701
LDHA GeneProduct ensembl:ENSG00000134333
SLC2A1 GeneProduct ensembl:ENSG00000117394
G6P Metabolite hmdb:HMDB0001401
erythroses Metabolite chebi:27904
Fructose 6P Metabolite chebi:15946
G6PD GeneProduct ensembl:ENSG00000160211
Transketolase Protein eccode:2.2.1.1
TALDO1 GeneProduct ensembl:ENSG00000177156
ATP Metabolite chebi:30616
ADP Metabolite chebi:16761
ATP Metabolite chebi:30616
ADP Metabolite chebi:16761
Glycogenolysis Pathway None
Glycogen Metabolite chebi:28087
Glycogenesis Pathway None
G6P Metabolite hmdb:HMDB0001401
PGK2 GeneProduct ensembl:ENSG00000170950

References