TCA cycle and deficiency of pyruvate dehydrogenase complex (PDHc) (WP2453)

Homo sapiens

When transported into the inner mitochondrial matrix, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase, PC (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH), the first enzyme of the PDH complex (PDHc). With a high cell-energy charge, co-enzyme A (CoA) is highly acylated, principally as acetyl-CoA, and able to obligately activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low, CoA is not acylated, therefore, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDHc and the TCA cycle to CO2 and H2O. The acetyl-CoA produced by the PDHc enters the TCA cycle and the reduced electron carriers (NADH and FADH2) that are generated during the oxidative reactions can then be used to drive ATP synthesis via oxidative phosphorylation. Description source: [ The Medical Biochemistryp Page] Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal].


M Aguirre , Martina Summer-Kutmon , Kristina Hanspers , Marianthi Kalafati , Denise Slenter , Eric Weitz , and Egon Willighagen


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Homo sapiens



Pathway Ontology

disease pathway pyruvate decarboxylase deficiency pathway citric acid cycle pathway


Label Type Compact URI Comment
ThPP Metabolite kegg.compound:C00068
Pyruvate Metabolite kegg.compound:C00022
Isocitrate Metabolite kegg.compound:C00311
Acetyl-CoA Metabolite kegg.compound:C00024
2-Hydroxy-ethyl-ThPP Metabolite kegg.compound:C05125
Oxalosuccinate Metabolite kegg.compound:C05379
Citrate Metabolite kegg.compound:C00158
Succinate Metabolite kegg.compound:C00042
Oxaloacetate Metabolite kegg.compound:C00036
Dihydro-lipoamide-E Metabolite chebi:80219
Lipoamide-E Metabolite kegg.compound:C15972
3-carboxy-1-hydroxypropyl-ThPP Metabolite pubchem.compound:440649
Succinoyl-CoA Metabolite kegg.compound:C00091
Phosphoenol-pyruvate Metabolite kegg.compound:C00074
(S)-Malate Metabolite kegg.compound:C00149
2-Oxo-glutarate Metabolite kegg.compound:C00026
S-Succinyl-dihydrolipoamide-E Metabolite kegg.compound:C16254
Fumarate Metabolite kegg.compound:C00122
S-Acetyldihydro-lipoamide-E Metabolite kegg.compound:C16255
ThPP Metabolite kegg.compound:C00068
Dihydro-lipoamide-E Metabolite chebi:80219
Lipoamide-E Metabolite kegg.compound:C15972
DLST GeneProduct ensembl:ENSG00000119689
DLD GeneProduct ensembl:ENSG00000091140
ACO1 GeneProduct ensembl:ENSG00000122729
FH GeneProduct ensembl:ENSG00000091483
MDH1 GeneProduct ensembl:ENSG00000014641
OGDH GeneProduct ensembl:ENSG00000105953
IDH1 GeneProduct ensembl:ENSG00000138413
PCK1 GeneProduct ensembl:ENSG00000124253
ACLY GeneProduct ensembl:ENSG00000131473
IDH1 GeneProduct ensembl:ENSG00000138413
CS GeneProduct ensembl:ENSG00000062485
SUCLG2 GeneProduct ensembl:ENSG00000172340
PDHA1 GeneProduct ensembl:ENSG00000131828
IDH3A GeneProduct ensembl:ENSG00000166411
SDHA GeneProduct ensembl:ENSG00000073578
PC GeneProduct ncbigene:5091
DLAT GeneProduct ensembl:ENSG00000150768
OGDH GeneProduct ensembl:ENSG00000105953
PDHA1 GeneProduct ensembl:ENSG00000131828
DLD GeneProduct ensembl:ENSG00000091140