CITRIC ACID CYCLE PATHWAY (PW:0000026)

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Description

The citric acid cycle, also known as the Krebs or tricarboxylic acid cycle (TCA), is considered a hub of cellular fuel metabolism. It consists of a series of eight reactions that oxidize the acetyl group of acetyl-CoA - the only precursor of the cycle - to two molecules of CO2 while conserving the liberated energy in the reduced NADH and FADH2 compounds. The stored electrons are passed to oxygen via the electron transport chain and the generated electrochemical gradien

Pathway Diagram:

Ariadne Genomics Inc. Aco2 Idh3 complex alpha-keto complex Scs complex Sdh complex Fh Mdh2 Cs succinyl-CoA alpha-ketoglutarate ---> succinyl-CoA isocitrate ---> alpha-ketoglutarate amino acid metabolic pathway gluconeogenesis pathway fatty acid biosynthetic pathway fatty acid beta degradation pathway ketone bodies metabolic pathway pyruvate metabolic pathway alpha-ketoglutarate <--> amino acid metabolic pathway FADH2 alpha-ketoglutarate succinate fumarate isocitrate malate <--> fumarate isocitrate <--> citrate glycolysis pathway isocitrate ---> NADH1 citrate oxaloacetate fumarate <--> succinate amino acid metabolic pathway <--> pyruvate amino acid metabolic pathway ---> succinyl-CoA succinyl-CoA <--> succinate oxaloacetate <--> amino acid metabolic pathway amino acid metabolic pathway ---> acetyl-CoA malate ---> NADH3 amino acid metabolic pathway ---> fumarate acetyl-CoA ---> citrate oxaloacetate ---> citrate succinate ---> FADH2 pyruvate ---> acetyl-CoA pyruvate malate alpha-ketoglutarate ---> NADH2 malate <--> oxaloacetate pyruvate ---> oxaloacetate fatty acid beta degradation pathway ---> acetyl-CoA acetyl-CoA acetyl-CoA <--> ketone bodies metabolic pathway citrate ---> fatty acid biosynthetic pathway glycolysis pathway ---> pyruvate NADH1 NADH2 NADH3 pyruvate ---> gluconeogenesis pathway
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Genes in Pathway:

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citric acid cycle pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Acly ATP citrate lyase JBrowse link 10 88,392,248 88,442,845 RGD:6907045
G Aco1 aconitase 1 JBrowse link 5 56,425,076 56,481,218 RGD:6907045
G Aco2 aconitase 2 JBrowse link 7 123,102,493 123,145,608 RGD:6907045
RGD:10402751
RGD:2306877
G Cs citrate synthase JBrowse link 7 2,752,680 2,778,963 RGD:6907045
RGD:10402751
RGD:2306828
RGD:2306877
G Dlat dihydrolipoamide S-acetyltransferase JBrowse link 8 55,062,549 55,087,832 RGD:6907045
RGD:10402751
G Dld dihydrolipoamide dehydrogenase JBrowse link 6 50,597,677 50,618,694 RGD:2306878
RGD:10402751
RGD:6907045
G Dlst dihydrolipoamide S-succinyltransferase JBrowse link 6 108,936,534 108,961,322 RGD:2306878
RGD:10402751
RGD:6907045
G Fh fumarate hydratase JBrowse link 13 93,651,486 93,677,371 RGD:2306828
RGD:10402751
G Idh1 isocitrate dehydrogenase (NADP(+)) 1, cytosolic JBrowse link 9 71,882,108 71,911,645 RGD:6907045
G Idh2 isocitrate dehydrogenase (NADP(+)) 2, mitochondrial JBrowse link 1 141,874,354 141,893,674 RGD:6907045
G Idh3a isocitrate dehydrogenase 3 (NAD+) alpha JBrowse link 8 59,164,601 59,183,899 RGD:2306828
RGD:10402751
RGD:6907045
G Idh3B isocitrate dehydrogenase 3 (NAD+) beta JBrowse link 3 122,808,564 122,813,638 RGD:2306828
RGD:10402751
RGD:6907045
G Idh3g isocitrate dehydrogenase 3 (NAD), gamma JBrowse link X 156,999,803 157,008,735 RGD:2306828
RGD:10402751
RGD:6907045
G Mdh1 malate dehydrogenase 1 JBrowse link 14 106,378,349 106,393,642 RGD:6907045
G Mdh2 malate dehydrogenase 2 JBrowse link 12 23,941,451 23,954,406 RGD:6907045
RGD:10402751
RGD:2306828
G Mpc1 mitochondrial pyruvate carrier 1 JBrowse link 1 53,026,608 53,038,229 RGD:10402751
G Ogdh oxoglutarate dehydrogenase JBrowse link 14 86,414,924 86,481,903 RGD:2306877
RGD:10402751
RGD:6907045
RGD:2306878
G Ogdhl oxoglutarate dehydrogenase-like JBrowse link 16 8,497,495 8,523,552 RGD:6907045
G Pc pyruvate carboxylase JBrowse link 1 219,759,157 219,859,854 RGD:6907045
RGD:10402751
G Pck1 phosphoenolpyruvate carboxykinase 1 JBrowse link 3 171,213,936 171,219,885 RGD:6907045
G Pck2 phosphoenolpyruvate carboxykinase 2 (mitochondrial) JBrowse link 15 34,216,735 34,224,357 RGD:6907045
G Pdha1 pyruvate dehydrogenase E1 alpha 1 subunit JBrowse link X 37,329,779 37,343,410 RGD:6907045
RGD:10402751
G Pdha2 pyruvate dehydrogenase E1 alpha 2 subunit JBrowse link 2 246,736,449 246,737,997 RGD:6907045
G Pdhb pyruvate dehydrogenase E1 beta subunit JBrowse link 15 18,540,826 18,546,855 RGD:6907045
RGD:10402751
G Sdha succinate dehydrogenase complex flavoprotein subunit A JBrowse link 1 31,545,631 31,570,601 RGD:2306881
RGD:10402751
RGD:6907045
G Sdhb succinate dehydrogenase complex iron sulfur subunit B JBrowse link 5 159,484,378 159,505,063 RGD:2306881
RGD:10402751
RGD:6907045
G Sdhc succinate dehydrogenase complex subunit C JBrowse link 13 89,498,047 89,518,979 RGD:2306881
RGD:10402751
RGD:6907045
G Sdhd succinate dehydrogenase complex subunit D JBrowse link 8 55,028,125 55,037,604 RGD:2306881
RGD:10402751
RGD:6907045
G Sucla2 succinate-CoA ligase ADP-forming beta subunit JBrowse link 15 55,461,695 55,516,954 RGD:2306915
RGD:6907045
G Suclg1 succinate-CoA ligase, alpha subunit JBrowse link 4 101,181,315 101,210,692 RGD:2306915
RGD:10402751
RGD:6907045
G Suclg2 succinate-CoA ligase, GDP-forming, beta subunit JBrowse link 4 127,552,100 127,824,970 RGD:2306915
RGD:10402751
RGD:6907045
altered citric acid cycle pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Fh fumarate hydratase JBrowse link 13 93,651,486 93,677,371 RGD:6907135
G Sdhb succinate dehydrogenase complex iron sulfur subunit B JBrowse link 5 159,484,378 159,505,063 RGD:6907134
G Sdhd succinate dehydrogenase complex subunit D JBrowse link 8 55,028,125 55,037,604 RGD:6907134

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Complexalpha keto complexalpha keto complex
ComplexIdh3 complexisocitrate dehydrogenase complex
ComplexSdh complexsuccinate dehydrogenase complex
ComplexScs ComplexSuccinyl-CoA synthetase complex catalyzes the reversible interconversion of succinyl-CoA and succinate and releases GTP or ATP.
ProteinPDB, October 2012 molecule of the month, TCA cycleThe structures of proteins/complexes of the eight reactions of the cycle, at the Protein Data Bank (the link is also provided at the end of the description)

Pathway Gene Annotations

Disease Annotations Associated with Genes in the citric acid cycle pathway
Disease TermsGene Symbols
2-hydroxyglutaricaciduriaIdh2
Abnormalities, MultipleDlat , Pdha1
adenoid cystic carcinomaIdh1
adult respiratory distress syndromeAco2 , Mdh1
Alpha-Ketoglutarate Dehydrogenase DeficiencyOgdh
Alzheimer's DiseasePck1
astrocytomaIdh1
Bardet-Biedl SyndromeMdh1
bladder urothelial carcinomaIdh1
Brain DiseasesMdh2
Brain IschemiaMdh2
Brain NeoplasmsIdh1 , Idh2
breast cancerIdh1
breast cancer, familialFh
Breast NeoplasmsIdh1
Burkitt LymphomaPc
Carcinoid Tumors, IntestinalSdhd
CarcinomaMdh2
Carcinoma, HepatocellularAcly , Aco2 , Idh1 , Idh2 , Pck1
Carcinoma, Renal CellFh , Pdhb , Sdhb , Sdhd
Carcinoma, Squamous Cell of Head and NeckIdh2
Carcinoma, Transitional CellIdh1
CardiomegalyIdh2
cardiomyopathyCs
cardiomyopathy, dilated, 1GGSdha
Cardiomyopathy, HypertrophicIdh2
Carney TriadSdha , Sdhb , Sdhc
Carney-Stratakis syndromeSdhb , Sdhc , Sdhd
carotid body tumorSdhd
Central Nervous System DiseasesIdh2
Charcot-Marie-Tooth DiseaseSdhc
Charcot-Marie-Tooth disease intermediate typeSdhc
Charcot-Marie-Tooth disease type 1BSdhc
Charcot-Marie-Tooth disease type 4ESdhc
Chemical and Drug Induced Liver InjuryMdh1
cholangiocarcinomaIdh1 , Idh2
ChondromaIdh1 , Idh2
Chronic Allograft NephropathyAco1
Chronic Cerebral HypoperfusionAco1
Colorectal NeoplasmsIdh1 , Idh2
Combined Oxidative Phosphorylation Deficiency 8Sdhd
congenital muscular dystrophySdhc
Congenital Thrombotic Disease, due to Protein C DeficiencyPc
Cowden diseaseSdhd
Cowden-Like SyndromeSdhb , Sdhd
Craniofacial AbnormalitiesIdh2
cutaneous malignant melanoma, susceptibility to, 1Pck1
D-2-hydroxyglutaric aciduriaIdh2
Developmental DisabilitiesAco2 , Sucla2
diabetes mellitus, experimentalPc , Pck1
Disease Models, AnimalIdh2 , Suclg2
Disease ProgressionIdh3B , Pdha1 , Suclg1
duodenal ulcerAco1
EnchondromatosisIdh1 , Idh2
EndometriosisSuclg2
EndotoxemiaPck1 , Pck2
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 51Mdh2
Fetal Growth RetardationPck1
Fumaric AciduriaFh
Gastrointestinal Stromal TumorsSdhb , Sdhc
Genetic Diseases, InbornAco2 , Dlat , Ogdhl , Pdha1
glioblastomaIdh1
gliomaIdh1 , Idh2
Growth DisordersIdh2
Heart FailureAcly , Cs , Mdh2 , Pck1
Heart Septal Defects, VentricularDlst
hemangiomaIdh1 , Idh2
Hereditary leiomyomatosis and renal cell cancerFh
Hereditary Paraganglioma-Pheochromocytoma SyndromesSdhb , Sdhc , Sdhd
HydronephrosisIdh2
Hypercholesterolemia, FamilialFh
HyperglycemiaPck1
HypertensionMdh1
HypoxiaCs , Pck2
Immunoblastic LymphadenopathyIdh2
Infantile Cerebellar-Retinal DegenerationAco2
lactic acidosisPdha1
Lactic Acidosis, Congenital Infantile, Due To LAD DeficiencyDld
Leigh DiseaseDld , Sdha
Leigh Syndrome due to Mitochondrial Complex II DeficiencySdha
Leigh Syndrome, X-LinkedPdha1
Leukemia, Myeloid, AcuteIdh1 , Idh2
Leukemia, Promyelocytic, AcuteIdh1 , Idh2
liver cancerIdh1
Liver Cirrhosis, ExperimentalMdh1 , Pc , Pck1 , Pck2
Liver NeoplasmsIdh1
lung adenocarcinomaIdh1 , Suclg2
Lymphoma, T-Cell, PeripheralIdh2
Mammary Neoplasms, AnimalMdh2
Mammary Neoplasms, ExperimentalMdh2
Maple Syrup Urine DiseaseDld
medulloblastomaIdh1
MelanomaIdh1 , Pck1 , Sdhd
Merkel cell carcinomaSdhd
Methylmalonic AcidemiaSuclg2
Mitochondrial Complex II DeficiencySdha , Sdhd
Mitochondrial Dna Depletion Syndrome 5 (Encephalomyopathic with or without Methylmalonic Aciduria)Sucla2
Mitochondrial DNA Depletion Syndrome 9 (Encephalomyopathic Type with Methylmalonic Aciduria)Suclg1
Mitochondrial Pyruvate Carrier DeficiencyMpc1
Multiple MyelomaIdh1 , Idh2
Muscular DiseasesSdha
Muscular DystrophiesSdhc
Myelodysplastic SyndromesIdh1 , Idh2
Myocardial InfarctionMdh2
Myocardial IschemiaDlat , Pdha1
Neoplasm InvasivenessAco1
Neoplasm Recurrence, LocalIdh1 , Idh2
Neoplastic Syndromes, HereditaryFh , Sdha , Sdhb , Sdhc , Sdhd
neurodegenerative diseaseAco2
nonalcoholic fatty liver diseaseAco1
obesityAcly , Cs , Idh1 , Pck1 , Sucla2 , Suclg2
oligodendrogliomaIdh1 , Idh2
Oligosynaptic InfertilityPdha2
Optic atrophy 8Aco2
Optic atrophy 9Aco2
OsteoarthritisAco1 , Idh2 , Idh3a , Pdha1 , Sdha
OsteoporosisIdh2
ParagangliomaSdhb , Sdhc , Sdhd
Paraganglioma, Extra-AdrenalSdhd
Paragangliomas 3Sdhc
Paragangliomas 4Sdhb
Paragangliomas 5Sdha
Paragangliomas with Sensorineural Hearing LossSdhd
Parkinson's DiseaseSdha
PheochromocytomaSdha , Sdhb , Sdhc , Sdhd
Phosphoenolpyruvate Carboxykinase 2 DeficiencyPck2
Phosphoenolpyruvate Carboxykinase DeficiencyPck1
PlasmacytomaIdh1
Pleomorphic Xanthoastrocytoma Dld , Mdh2 , Ogdh
Precursor Cell Lymphoblastic Leukemia-LymphomaIdh1
prostate adenocarcinomaIdh1
prostate cancerDlat
prostatic neoplasmsPdha1
Pyruvate Carboxylase Deficiency DiseasePc
Pyruvate Dehydrogenase Complex Deficiency DiseaseDlat , Dld , Pdha1 , Pdhb
Pyruvate Dehydrogenase E1 Alpha DeficiencyPdha1
Pyruvate Dehydrogenase E1-Beta DeficiencyPdhb
Pyruvate Dehydrogenase E2 DeficiencyDlat
Pyruvate Metabolism, Inborn ErrorsPdha1
renal carcinomaSdhb
Renal InsufficiencyIdh2
Retinitis PigmentosaIdh3B
Retinitis Pigmentosa 46Idh3B
SeizuresIdh2 , Pdha1
sleep deprivationDlat
Smith-Magenis syndromeAcly
Stargardt diseaseFh
Stargardt disease 1Fh
Stomach NeoplasmsIdh3B , Pdha1 , Suclg1
Substance-Related DisordersMpc1
Thrombophilia, Hereditary, due to Protein C Deficiency, Autosomal RecessivePc
Tumor Predisposition SyndromeFh , Sdha , Sdhb , Sdhc , Sdhd
type 2 diabetes mellitusPc , Pck1
Ventricular Dysfunction, LeftIdh2
Pathway Annotations Associated with Genes in the citric acid cycle pathway
Pathway TermsGene Symbols
2-aminoadipic 2-oxoadipic aciduria pathwayDld , Dlst
3-hydroxy-3-methylglutaryl-CoA lyase deficiency pathwayDld
3-hydroxyisobutyric aciduria pathwayDld
3-methylcrotonyl CoA carboxylase 1 deficiency pathwayDld
3-methylglutaconic aciduria type 1 pathwayDld
3-methylglutaconic aciduria type 3 pathwayDld
alanine metabolic pathwayPc
altered citric acid cycle pathwayFh , Sdhb , Sdhd
Alzheimer's disease pathwaySdha , Sdhb , Sdhc , Sdhd
butanoate metabolic pathwayPdha1 , Pdha2 , Pdhb
citric acid cycle pathwayAcly , Aco1 , Aco2 , Cs , Dlat , Dld , Dlst , Fh , Idh1 , Idh2 , Idh3a , Idh3B , Idh3g , Mdh1 , Mdh2 , Mpc1 , Ogdh , Ogdhl , Pc , Pck1 , Pck2 , Pdha1 , Pdha2 , Pdhb , Sdha , Sdhb , Sdhc , Sdhd , Sucla2 , Suclg1 , Suclg2
dihydropyrimidine dehydrogenase deficiency pathwayDld
dimethylglycine dehydrogenase deficiency pathwayDld
doxorubicin response pathwayAco1
eicosanoid signaling pathway via peroxisome proliferator-activated receptor gammaPck1 , Pck2
electron transport chain pathwaySdha , Sdhb , Sdhc , Sdhd
fatty acid biosynthetic pathwayAcly
folate cycle metabolic pathwayDld
forkhead class A signaling pathwayPck1
fructose-1,6-bisphosphatase deficiency pathwayMdh2 , Mpc1 , Pc , Pck1
fumaric aciduria pathwayAco2 , Cs , Dlat , Dld , Dlst , Fh , Idh3a , Idh3B , Idh3g , Mdh2 , Mpc1 , Ogdh , Pc , Pdha1 , Pdhb , Sdha , Sdhb , Sdhc , Sdhd , Suclg1 , Suclg2
gluconeogenesis pathwayDlat , Dld , Mdh2 , Mpc1 , Pc , Pck1 , Pck2 , Pdha1 , Pdha2 , Pdhb
glutaric aciduria type I pathwayDld , Dlst
glutathione metabolic pathwayIdh1 , Idh2
glycine, serine and threonine metabolic pathwayDld
glycogen storage disease type Ia pathwayMdh2 , Mpc1 , Pc , Pck1
glycogen storage disease type Ib pathwayMdh2 , Mpc1 , Pc , Pck1
glycolysis pathwayDlat , Dld , Pck1 , Pck2 , Pdha1 , Pdha2 , Pdhb
glycolysis/gluconeogenesis pathwayDlat , Dld , Pck1 , Pck2 , Pdha1 , Pdha2 , Pdhb
glyoxylate and dicarboxylate metabolic pathwayAco1 , Aco2 , Cs , Mdh1 , Mdh2
Huntington's disease pathwaySdha , Sdhb , Sdhc , Sdhd
hyperlysinemia pathwayDld , Dlst
insulin signaling pathwayPck1 , Pck2
iron homeostasis pathwayAco1
isobutyryl-CoA dehydrogenase deficiency pathwayDld
isovaleric acidemia pathwayDld
lactic acidosis pathwayPc
Leigh disease pathwayDlat , Dld , Mdh1 , Pc , Pck1 , Pdha1 , Pdhb
lysine degradation pathwayDld , Dlst , Ogdh , Ogdhl
malonic aciduria pathwayDld
maple syrup urine disease pathwayDld
methylmalonate semialdehyde dehydrogenase deficiency pathwayDld
methylmalonic acidemia pathwayDld
methylmalonic aciduria, cobalamin-related pathwayDld
mitochondrial complex II deficiency pathwayAco2 , Cs , Dlat , Dld , Dlst , Fh , Idh3a , Idh3B , Idh3g , Mdh2 , Mpc1 , Ogdh , Pc , Pdha1 , Pdhb , Sdha , Sdhb , Sdhc , Sdhd , Suclg1 , Suclg2
nicotinamide adenine dinucleotide metabolic pathwayMdh1 , Mdh2
nonketotic hyperglycinemia pathwayDld
oxidative phosphorylation pathwaySdha , Sdhb , Sdhc , Sdhd
Parkinson's disease pathwaySdha , Sdhb , Sdhc , Sdhd
phosphoenolpyruvate carboxykinase deficiency pathwayMdh2 , Mpc1 , Pc , Pck1
primary hyperoxaluria type 1 pathwayPc
primary hyperoxaluria type 2 pathwayDlat , Dld , Mdh1 , Pc , Pck1 , Pdha1 , Pdhb
propanoate metabolic pathwayDld , Sucla2 , Suclg1 , Suclg2
propionic acidemia pathwayDld
pyruvate carboxylase deficiency pathwayPc
pyruvate decarboxylase deficiency pathwayDlat , Dld , Mdh1 , Pc , Pck1 , Pdha1 , Pdhb
pyruvate dehydrogenase E1 deficiency pathwayDlat , Dld , Mdh1 , Pc , Pck1 , Pdha1 , Pdhb
pyruvate dehydrogenase E2 deficiency pathwayAco2 , Cs , Dlat , Dld , Dlst , Fh , Idh3a , Idh3B , Idh3g , Mdh2 , Mpc1 , Ogdh , Pc , Pdha1 , Pdhb , Sdha , Sdhb , Sdhc , Sdhd , Suclg1 , Suclg2
pyruvate dehydrogenase E3 deficiency pathwayAco2 , Cs , Dlat , Dld , Dlst , Fh , Idh3a , Idh3B , Idh3g , Mdh2 , Mpc1 , Ogdh , Pc , Pdha1 , Pdhb , Sdha , Sdhb , Sdhc , Sdhd , Suclg1 , Suclg2
pyruvate kinase deficiency of red cells pathwayDlat , Dld , Mdh1 , Pc , Pck1 , Pdha1 , Pdhb
pyruvate metabolic pathwayDlat , Dld , Mdh1 , Mdh2 , Pc , Pck1 , Pck2 , Pdha1 , Pdha2 , Pdhb
renal cell carcinoma pathwayFh , Sdhb , Sdhd
saccharopinuria pathwayDld , Dlst
sarcosinemia pathwayDld
triosephosphate isomerase deficiency pathwayMdh2 , Mpc1 , Pc , Pck1
tryptophan metabolic pathwayOgdh , Ogdhl
valine, leucine and isoleucine biosynthetic pathwayPdha1 , Pdha2 , Pdhb
valine, leucine and isoleucine degradation pathwayDld

References Associated with the citric acid cycle pathway:

Ontology Path Diagram:

paths to the root

Import into Pathway Studio: