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: [https://themedicalbiochemistrypage.org/tca-cycle.php The Medical Biochemistryp Page] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2453 CPTAC Assay Portal]. disease pathway PW:0000013 Pathway Ontology pyruvate dehydrogenase complex deficiency pathway PW:0001752 Pathway Ontology citric acid cycle pathway PW:0000026 Pathway Ontology