ENTRY hsa00020 Pathway NAME Citrate cycle (TCA cycle) - Homo sapiens (human) DESCRIPTION The citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form of acetate, derived from glycolysis and pyruvate oxidation for carbohydrates and from beta oxidation of fatty acids. The two-carbon acetyl group in acetyl-CoA is transferred to the four-carbon compound of oxaloacetate to form the six-carbon compound of citrate. In a series of reactions two carbons in citrate are oxidized to CO2 and the reaction pathway supplies NADH for use in the oxidative phosphorylation and other metabolic processes. The pathway also supplies important precursor metabolites including 2-oxoglutarate. At the end of the cycle the remaining four-carbon part is transformed back to oxaloacetate. According to the genome sequence data, many organisms seem to lack genes for the full cycle [MD:M00009], but contain genes for specific segments [MD:M00010 M00011]. CLASS Metabolism; Carbohydrate metabolism PATHWAY_MAP hsa00020 Citrate cycle (TCA cycle) MODULE hsa_M00003 Gluconeogenesis, oxaloacetate => fructose-6P [PATH:hsa00020] hsa_M00009 Citrate cycle (TCA cycle, Krebs cycle) [PATH:hsa00020] hsa_M00010 Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate [PATH:hsa00020] hsa_M00011 Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate [PATH:hsa00020] hsa_M00307 Pyruvate oxidation, pyruvate => acetyl-CoA [PATH:hsa00020] NETWORK nt06024 Valine, leucine and isoleucine degradation nt06031 Citrate cycle and pyruvate metabolism nt06032 Lipoic acid metabolism ELEMENT N01603 Pyruvate oxidation N01604 Citrate cycle, first carbon oxidation N01609 Citrate cycle, second carbon oxidation 1 N01616 Dihydrolipoamide dehydrogenase N01617 Citrate cycle, second carbon oxidation 2 DRUG D10691 Bempedoic acid (JAN/USAN/INN) D11090 Ivosidenib (JAN/USAN/INN) D11834 Vorasidenib (USAN/INN) D11835 Vorasidenib citrate (USAN) D12483 Olutasidenib (USAN/INN) D12708 Crelosidenib (USAN) D12717 Crelosidenib gentisate (USAN) DBLINKS GO: 0006099 ORGANISM Homo sapiens (human) [GN:hsa] GENE 1431 CS; citrate synthase [KO:K01647] [EC:2.3.3.1] 1737 DLAT; dihydrolipoamide S-acetyltransferase [KO:K00627] [EC:2.3.1.12] 1738 DLD; dihydrolipoamide dehydrogenase [KO:K00382] [EC:1.8.1.4] 1743 DLST; dihydrolipoamide S-succinyltransferase [KO:K00658] [EC:2.3.1.61] 2271 FH; fumarate hydratase [KO:K01679] [EC:4.2.1.2] 3417 IDH1; isocitrate dehydrogenase (NADP(+)) 1 [KO:K00031] [EC:1.1.1.42] 3418 IDH2; isocitrate dehydrogenase (NADP(+)) 2 [KO:K00031] [EC:1.1.1.42] 3419 IDH3A; isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha [KO:K00030] [EC:1.1.1.41] 3420 IDH3B; isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta [KO:K00030] [EC:1.1.1.41] 3421 IDH3G; isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma [KO:K00030] [EC:1.1.1.41] 4190 MDH1; malate dehydrogenase 1 [KO:K00025] [EC:1.1.1.37] 4191 MDH2; malate dehydrogenase 2 [KO:K00026] [EC:1.1.1.37] 47 ACLY; ATP citrate lyase [KO:K01648] [EC:2.3.3.8] 48 ACO1; aconitase 1 [KO:K01681] [EC:4.2.1.3] 4967 OGDH; oxoglutarate dehydrogenase [KO:K00164] [EC:1.2.4.2] 50 ACO2; aconitase 2 [KO:K01681] [EC:4.2.1.3] 5091 PC; pyruvate carboxylase [KO:K01958] [EC:6.4.1.1] 5105 PCK1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32] 5106 PCK2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32] 5160 PDHA1; pyruvate dehydrogenase E1 subunit alpha 1 [KO:K00161] [EC:1.2.4.1] 5161 PDHA2; pyruvate dehydrogenase E1 subunit alpha 2 [KO:K00161] [EC:1.2.4.1] 5162 PDHB; pyruvate dehydrogenase E1 subunit beta [KO:K00162] [EC:1.2.4.1] 55753 OGDHL; oxoglutarate dehydrogenase L [KO:K00164] [EC:1.2.4.2] 6389 SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234] [EC:1.3.5.1] 6390 SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235] [EC:1.3.5.1] 6391 SDHC; succinate dehydrogenase complex subunit C [KO:K00236] 6392 SDHD; succinate dehydrogenase complex subunit D [KO:K00237] 8801 SUCLG2; succinate-CoA ligase GDP-forming subunit beta [KO:K01900] [EC:6.2.1.4 6.2.1.5] 8802 SUCLG1; succinate-CoA ligase GDP/ADP-forming subunit alpha [KO:K01899] [EC:6.2.1.4 6.2.1.5] 8803 SUCLA2; succinate-CoA ligase ADP-forming subunit beta [KO:K01900] [EC:6.2.1.4 6.2.1.5] COMPOUND C00022 Pyruvate C00024 Acetyl-CoA C00026 2-Oxoglutarate C00036 Oxaloacetate C00042 Succinate C00068 Thiamin diphosphate C00074 Phosphoenolpyruvate C00091 Succinyl-CoA C00122 Fumarate C00149 (S)-Malate C00158 Citrate C00311 Isocitrate C00417 cis-Aconitate C05125 2-(alpha-Hydroxyethyl)thiamine diphosphate C05379 Oxalosuccinate C05381 3-Carboxy-1-hydroxypropyl-ThPP C15972 Enzyme N6-(lipoyl)lysine C15973 Enzyme N6-(dihydrolipoyl)lysine C16254 [Dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine C16255 [Dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine REFERENCE AUTHORS Nishizuka Y (ed). TITLE [Metabolic Maps] (In Japanese) JOURNAL Tokyo Kagaku Dojin (1980) REFERENCE AUTHORS Nishizuka Y, Seyama Y, Ikai A, Ishimura Y, Kawaguchi A (eds). TITLE [Cellular Functions and Metabolic Maps] (In Japanese) JOURNAL Tokyo Kagaku Dojin (1997) REFERENCE AUTHORS Michal G. TITLE Biochemical Pathways JOURNAL Wiley (1999) REL_PATHWAY hsa00010 Glycolysis / Gluconeogenesis hsa00053 Ascorbate and aldarate metabolism hsa00061 Fatty acid biosynthesis hsa00062 Fatty acid elongation hsa00071 Fatty acid degradation hsa00190 Oxidative phosphorylation hsa00220 Arginine biosynthesis hsa00250 Alanine, aspartate and glutamate metabolism hsa00280 Valine, leucine and isoleucine degradation hsa00350 Tyrosine metabolism hsa00470 D-Amino acid metabolism hsa00630 Glyoxylate and dicarboxylate metabolism KO_PATHWAY ko00020 ///