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]
DRUG        D10691  Bempedoic acid (JAN/USAN/INN)
            D11090  Ivosidenib (JAN/USAN/INN)
            D11834  Vorasidenib (USAN/INN)
            D11835  Vorasidenib citrate (USAN)
            D12483  Olutasidenib (USAN/INN)
DBLINKS     GO: 0006099
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        1431  CS; citrate synthase [KO:K01647] [EC:2.3.3.1]
            47  ACLY; ATP citrate lyase [KO:K01648] [EC:2.3.3.8]
            50  ACO2; aconitase 2 [KO:K01681] [EC:4.2.1.3]
            48  ACO1; aconitase 1 [KO:K01681] [EC:4.2.1.3]
            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]
            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]
            3419  IDH3A; isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha [KO:K00030] [EC:1.1.1.41]
            55753  OGDHL; oxoglutarate dehydrogenase L [KO:K00164] [EC:1.2.4.2]
            4967  OGDH; oxoglutarate dehydrogenase [KO:K00164] [EC:1.2.4.2]
            1743  DLST; dihydrolipoamide S-succinyltransferase [KO:K00658] [EC:2.3.1.61]
            1738  DLD; dihydrolipoamide dehydrogenase [KO:K00382] [EC:1.8.1.4]
            8802  SUCLG1; succinate-CoA ligase GDP/ADP-forming subunit alpha [KO:K01899] [EC:6.2.1.4 6.2.1.5]
            8801  SUCLG2; succinate-CoA ligase GDP-forming subunit beta [KO:K01900] [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]
            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]
            2271  FH; fumarate hydratase [KO:K01679] [EC:4.2.1.2]
            4190  MDH1; malate dehydrogenase 1 [KO:K00025] [EC:1.1.1.37]
            4191  MDH2; malate dehydrogenase 2 [KO:K00026] [EC:1.1.1.37]
            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]
            5161  PDHA2; pyruvate dehydrogenase E1 subunit alpha 2 [KO:K00161] [EC:1.2.4.1]
            5160  PDHA1; pyruvate dehydrogenase E1 subunit alpha 1 [KO:K00161] [EC:1.2.4.1]
            5162  PDHB; pyruvate dehydrogenase E1 subunit beta [KO:K00162] [EC:1.2.4.1]
            1737  DLAT; dihydrolipoamide S-acetyltransferase [KO:K00627] [EC:2.3.1.12]
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
///
