The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It is the most important metabolic pathway for the energy supply to the body. TCA is the most important central pathway connecting almost all the individual metabolic pathways. Oxalacetic acid and GTP are catalyzed by phosphoenolypyruvate carboxykinase to form GDP, CO2, and phosphoenolpyruvic acid. This is a single direction reaction occurring outside of the mitochondria. Phosphoenolpyruvic acid then becomes part of the glycolysis/ gluconeogenesis processes outside of the mitochondria which will then produce pyruvic acid that will be trans-located back into the mitochondria. Within the mitochondria, the single direction reaction of pyruvic acid, ATP, and hydrogen carbonate catalyzed by pyruvate carboxylase 1 produces phosphate, ADP, and oxalacetic acid. Pyruvic acid and lipoamide-E are catalyzed by probable pyruvate dehydrogenase E1 component subunit alpha and pyruvate dehydrogenase E1 component subunit beta, mitochondrial to form CO2 and S-acetyldihydrolipoamide-E in a single direction reaction in the mitochondria. S-Acetyldihydrolipoamide-E and CoA are catalyzed by dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex and (R)-lipoic acid to form dihydrolipoamide-E and acetyl-CoA. This is a bi-directional reaction occurring in the mitochondria. Acetyl-CoA is an input compound in the fatty acid biosynthesis and fatty acid elongation in mitochondria sub-pathways, as well as an output compound in the fatty acid metabolism and Val, Leu & Ile degradation sub-pathways. Dihydrolipoamide-E and NAD are catalyzed by dihydrolipoyl dehydrogenase to produce NADH, H+, and lipoamide-E through a bi-directional reaction in the mitochondria. Oxalacetic acid, H2O, and acetyl-CoA are catalyzed by probable ATP-citrate synthase and probable citrate synthase to form CoA and citric acid in a bi-directional reaction in the mitochondria. Oxalacetic acid is an input and output compound in the sub-pathways alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism within the mitochondria. Citric acid is catalyzed by probable cytoplasmic aconitate hydratase to form H2O and cis-aconitic acid, which are then catalyzed again by probable cytoplasmic aconitate hydratase to form isocitric acid. This is a bi-directional reaction in the mitochondria. Isocitric acid is involved in two bi-directional reactions in the mitochondria to form 2- oxoglutaric acid. The first reaction is between isocitric acid and NADP+ catalyzed by isocitrate dehydrogenase [NADP] to produce NADPH, H+, and oxalosuccinic acid. Oxalosuccinic acid is then catalyzed by isocitrate dehydrogenase [NADP] to form CO2 and 2-oxoglutaric acid. The other reaction is between isocitric acid and NAD catalyzed by probable isocitrate dehydrogenase [NAD] subunit alpha, probable isocitrate dehydrogenase [NAD] subunit beta, and magnesium to produce NADH, CO2, H+, and 2-oxoglutaric acid. Oxoglutaric acid is an input compound in the sub-pathway arginine biosynthesis, as well as an input and output compound in the sub-pathways D-Gin & D-Glu metabolism, ascorbate and aldarate metabolism, and alanine, aspartate and glutamate metabolism. In a single direction reaction, oxoglutaric acid and lipoamide-E are catalyzed by 2-oxoglutarate dehydrogenase to form CO2 and S-Succinyldihydrolipoamide-E. S-Succinyldihydrolipoamide-E and CoA are catalyzed by dihydrolipoamide S-Succinyltransferase to produce dihydrolipoamide-E and succinyl-CoA in a bi-directional reaction in the mitochondria. Dihydrolipoamide-E and NAD catalyzed by dihydrolipoyl dehydrogenase produce NADH, H+, and lipoamide-E in a bi-directional reaction. Succinyl-CoA, GDP, and phosphate are catalyzed by succinate--CoA ligase [ADP/GDP-forming] subunit alpha and succinate--CoA ligase [GDP-forming] subunit beta to form CoA, GTP, and succinic acid through a bi-directional reaction. Succinyl-CoA is also an output compound of the sub-pathway Val, Leu & Ile degradation. In another bi-directional reaction, succinic acid and a quinone are catalyzed by succinate dehydrogenase [ubiquinone] flavoprotein subunit and FAD to produce a hydroquinone and fumaric acid. Fumaric acid is an input and output compound in the sub-pathways arginine biosynthesis and tyrosine metabolism within the mitochondria. Fumaric acid and H2O are catalyzed by probable fumarate hydratase to produce L-Malic acid in a bi-directional reaction. L-malic acid and NAD are catalyzed by probable malate dehydrogenase to produce NADH, H+, and oxalacetic acid through a bi-directional reaction.

Citrate Cycle References