CITRIC ACID CYCLE PATHWAY (PW:0000026)
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 gradient is used to drive the ATP synthesis.
The acetyl-CoA necessary to initiate the cycle is derived from pyruvate or from
fatty acids and amino acid degradation. The cycle intermediates can also be
derived from or fueled into other pathways. Oxaloacetate, alpha-ketoglutarate,
succinyl-CoA and fumarate can be derived from the degradation of various amino
acids. Oxaloacetate can be used for the biosynthesis of glucose and amino
acids, alpha-ketoglutarate for the biosynthesis of amino acids and citrate
provides the source for the cytosolic acetyl CoA in the fatty acids
biosynthetic pathway. One round of the cycle gives rise to three molecules of
NADH and one of FADH
2 (colored gold and as applicable, numbered); there
is also one molecule of GTP or ATP produced (not shown). The oxaloacetate
consumed in the first step is regenerated in the last step; the cycle can go on
for as long as there are acetyl groups available. One turn of the cycle
generates ~10 ATP molecules. Glucose oxidation requires two rounds of the cycle
(glycolysis yields two pyruvate molecules whose oxidation produces two acetyl-CoAs).
More rounds of the TCA cycle are necessary
to complete oxidation of fatty acids since their carbon skeletons are larger than that
of glucose. The flux of the cycle is controlled by the availability of
substrates, product inhibition and competitive feedback inhibition. The cycle takes
place in the mitochondrion. Since the metabolites are present in both
mitochondria and cytosol, the identification of rate-limiting steps is more
difficult. The estimated free energy changes for the reactions point to three
enzymes likely to function far from equilibrium: citrate synthase (step 1),
isocitrate dehydrogenase (step 3) and oxoglutarate dehydrogenase (step 4) - the
unidirectional reaction arrows in the diagram.
Click to get to the entry for the molecule of the month, October 2012, at the Protein Data Bank which is dedicated to the structures of proteins/complexes in the eight reactions of the cycle. To see the ontology report for annotations, GViewer and download, click
here [click
to see the ontology report for associated GO term -
GO:0006099 , KEGG map -
map00020 and related entry at Reactome - REACT_1046.3 ]...(less)
Pathway Diagram:
Genes in Pathway:
G
Acly
ATP citrate lyase
IEA
KEGG rno:00020
NCBI chr10:85,412,045...85,464,253
G
Aco1
aconitase 1
IEA
KEGG rno:00020
NCBI chr 5:55,259,841...55,315,872
G
Aco2
aconitase 2
IEA ISO IDA
KEGG SMPDB PMID:9712727 SMP:00057 rno:00020, RGD:2306877
NCBI chr 7:113,385,677...113,428,794
G
Cs
citrate synthase
IEA ISO IDA
KEGG SMPDB PMID:9712727 SMP:00057 rno:00020, RGD:2306877
NCBI chr 7:758,074...791,421
G
Dlat
dihydrolipoamide S-acetyltransferase
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr 8:59,875,537...59,900,947
G
Dld
dihydrolipoamide dehydrogenase
ISO IEA
SMPDB KEGG PMID:10672230 SMP:00057 rno:00020, RGD:2306878
NCBI chr 6:53,631,686...53,655,059
G
Dlst
dihydrolipoamide S-succinyltransferase
ISO IEA
SMPDB KEGG PMID:10672230 SMP:00057 rno:00020, RGD:2306878
NCBI chr 6:104,758,511...104,783,296
G
Fh
fumarate hydratase
ISO
SMPDB SMP:00057
NCBI chr13:87,524,331...87,550,215
G
Idh1
isocitrate dehydrogenase (NADP(+)) 1
IEA
KEGG rno:00020
NCBI chr 9:66,534,146...66,563,703
G
Idh2
isocitrate dehydrogenase (NADP(+)) 2
IEA
KEGG rno:00020
NCBI chr 1:134,038,644...134,057,969
G
Idh3a
isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr 8:54,971,694...54,991,085
G
Idh3b
isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr 3:117,481,845...117,486,909
G
Idh3g
isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr X:156,666,573...156,675,482
G
Mdh1
malate dehydrogenase 1
IEA
KEGG rno:00020
NCBI chr14:95,630,625...95,645,920
G
Mdh2
malate dehydrogenase 2
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr12:26,530,886...26,543,841
G
Mpc1
mitochondrial pyruvate carrier 1
ISO
SMPDB SMP:00057
NCBI chr 1:52,437,745...52,449,399
G
Ogdh
oxoglutarate dehydrogenase
IDA ISO IEA
SMPDB KEGG PMID:9712727 PMID:10672230 SMP:00057 rno:00020, RGD:2306877 , RGD:2306878
NCBI chr14:81,150,021...81,217,479
G
Ogdhl
oxoglutarate dehydrogenase L
IEA
KEGG rno:00020
NCBI chr16:7,578,343...7,604,385
G
Pc
pyruvate carboxylase
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr 1:201,799,374...201,898,412
G
Pck1
phosphoenolpyruvate carboxykinase 1
IEA
KEGG rno:00020
NCBI chr 3:161,930,256...161,936,205
G
Pck2
phosphoenolpyruvate carboxykinase 2 (mitochondrial)
IEA
KEGG rno:00020
NCBI chr15:32,997,853...33,006,691
G
Pdha1
pyruvate dehydrogenase E1 subunit alpha 1
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr X:38,509,158...38,522,986
G
Pdha2
pyruvate dehydrogenase E1 subunit alpha 2
IEA
KEGG rno:00020
NCBI chr 2:229,872,300...229,873,848
G
Pdhb
pyruvate dehydrogenase E1 subunit beta
IEA ISO
KEGG SMPDB SMP:00057 rno:00020
NCBI chr15:19,182,789...19,188,731
G
Sdha
succinate dehydrogenase complex flavoprotein subunit A
ISO IEA
SMPDB KEGG PMID:16143825 SMP:00057 rno:00020, RGD:2306881
NCBI chr 1:28,935,965...28,960,936
G
Sdhb
succinate dehydrogenase complex iron sulfur subunit B
ISO IEA
SMPDB KEGG PMID:16143825 SMP:00057 rno:00020, RGD:2306881
NCBI chr 5:153,264,906...153,285,570
G
Sdhc
succinate dehydrogenase complex subunit C
ISO IEA
SMPDB KEGG PMID:16143825 SMP:00057 rno:00020, RGD:2306881
NCBI chr13:83,544,652...83,565,560
G
Sdhd
succinate dehydrogenase complex subunit D
ISO IEA
SMPDB KEGG PMID:16143825 SMP:00057 rno:00020, RGD:2306881
NCBI chr 8:59,841,090...59,850,641
G
Sucla2
succinate-CoA ligase ADP-forming subunit beta
IDA IEA
KEGG PMID:17403370 rno:00020, RGD:2306915
NCBI chr15:48,752,356...48,805,495
G
Suclg1
succinate-CoA ligase GDP/ADP-forming subunit alpha
IDA ISO IEA
SMPDB KEGG PMID:17403370 SMP:00057 rno:00020, RGD:2306915
NCBI chr 4:105,308,236...105,337,595
G
Suclg2
succinate-CoA ligase GDP-forming subunit beta
IDA ISO IEA
SMPDB KEGG PMID:17403370 SMP:00057 rno:00020, RGD:2306915
NCBI chr 4:128,067,031...128,337,146
G
Fh
fumarate hydratase
ISO
RGD
PMID:17211469 RGD:6907135
NCBI chr13:87,524,331...87,550,215
G
Sdhb
succinate dehydrogenase complex iron sulfur subunit B
ISO
RGD
PMID:21771581 RGD:6907134
NCBI chr 5:153,264,906...153,285,570
G
Sdhd
succinate dehydrogenase complex subunit D
ISO
RGD
PMID:21771581 RGD:6907134
NCBI chr 8:59,841,090...59,850,641
Pathway Gene Annotations
Disease Annotations Associated with Genes in the citric acid cycle pathway
Acly congestive heart failure , hepatocellular carcinoma , obesity Aco1 Chronic Allograft Nephropathy , Chronic Cerebral Hypoperfusion , duodenal ulcer , metabolic dysfunction-associated steatotic liver disease , Neoplasm Invasiveness , osteoarthritis Aco2 acute intermittent porphyria , adenylosuccinase lyase deficiency , adult respiratory distress syndrome , common variable immunodeficiency 4 , COVID-19 , Developmental Disabilities , fundus dystrophy , genetic disease , hepatocellular carcinoma , infantile cerebellar-retinal degeneration , mitochondrial metabolism disease , optic atrophy , optic atrophy 9 , Rubinstein-Taybi syndrome Cs atrial fibrillation , bipolar disorder , Brain Hypoxia-Ischemia , Cardiomegaly , cardiomyopathy , Chronic Allograft Nephropathy , congestive heart failure , dilated cardiomyopathy , Endotoxemia , Experimental Diabetes Mellitus , hyperthyroidism , hypertrophic cardiomyopathy , hypothyroidism , Hypoxia , limb ischemia , Liver Reperfusion Injury , myocardial infarction , obesity , Sepsis , Ventricular Dysfunction, Left Dlat ataxia telangiectasia , BH4-deficient hyperphenylalaninemia A , Carney-Stratakis syndrome , Chemical and Drug Induced Liver Injury , chromosome 11 partial duplication syndrome , congenital disorder of glycosylation Il , dilated cardiomyopathy 1II , genetic disease , intellectual disability , Leigh disease , Myocardial Ischemia , prostate cancer , Pyruvate Dehydrogenase E2 Deficiency , Sleep Deprivation Dld Congenital Infantile Lactic Acidosis due to LAD Deficiency , genetic disease , lactic acidosis , Leigh disease , lissencephaly 5 , maple syrup urine disease , pleomorphic xanthoastrocytoma , pyruvate decarboxylase deficiency , Subacute Necrotizing Encephalopathy of Leigh, Infantile Dlst Alzheimer's disease , Hereditary Paraganglioma-Pheochromocytoma Syndromes , intellectual disability , oxoglutarate dehydrogenase deficiency , paraganglioma , Paragangliomas 7 Fh B-lymphoblastic leukemia/lymphoma , breast cancer , COVID-19 , fumarase deficiency , gastrointestinal stromal tumor , hepatoblastoma , hepatocellular carcinoma , Hereditary Leiomyomatosis and Renal Cell Cancer , Hereditary Neoplastic Syndromes , leiomyoma cutis , lung non-small cell carcinoma , Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 , microcephaly , Neurodevelopmental Disorders , ovarian cancer , parathyroid carcinoma , renal cell carcinoma , spinocerebellar ataxia 45 , uterine fibroid Idh1 Acute Liver Failure , acute lymphoblastic leukemia , acute myeloid leukemia , acute promyelocytic leukemia , adenoid cystic carcinoma , autoimmune disease , Brain Neoplasms , Breast Neoplasms , cholangiocarcinoma , Cholangiofibrosis , chondroma , COVID-19 , diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype , glioblastoma , hemangioma , hepatocellular carcinoma , hepatocellular clear cell carcinoma , high grade glioma , intrahepatic cholangiocarcinoma , lung adenocarcinoma , lung squamous cell carcinoma , lymphoma , Maffucci syndrome , myelodysplastic syndrome , Neoplasm Recurrence, Local , Neurodevelopmental Disorders , obesity , oligodendroglioma , Ollier disease , paroxysmal extreme pain disorder , primary pulmonary hypertension , prostate adenocarcinoma , Prostatic Neoplasms , skin melanoma Idh2 2-hydroxyglutaric aciduria , acute myeloid leukemia , acute myocardial infarction , acute promyelocytic leukemia , Animal Disease Models , Bloom syndrome , bone remodeling disease , Cardiomegaly , central nervous system disease , Chemical and Drug Induced Liver Injury , cholangiocarcinoma , chondroma , colorectal cancer , Craniofacial Abnormalities , D-2-hydroxyglutaric aciduria , D-2-hydroxyglutaric aciduria 2 , esophagus squamous cell carcinoma , genetic disease , Growth Disorders , hemangioma , hepatocellular carcinoma , hepatocellular clear cell carcinoma , hydronephrosis , hypertrophic cardiomyopathy , Immunoblastic Lymphadenopathy , intrahepatic cholangiocarcinoma , kidney failure , Liver Reperfusion Injury , lung adenocarcinoma , lung cancer , lung non-small cell carcinoma , lung squamous cell carcinoma , Maffucci syndrome , metabolic dysfunction-associated steatohepatitis , metabolic dysfunction-associated steatotic liver disease , Metabolic Syndrome , mitochondrial metabolism disease , myelodysplastic syndrome , Neoplasm Recurrence, Local , oligodendroglioma , Ollier disease , osteoarthritis , osteoporosis , peripheral T-cell lymphoma , status epilepticus , stomach cancer , teratoma , Vascular Malformations , Ventricular Dysfunction, Left Idh3a Bloom syndrome , colorectal cancer , fundus dystrophy , osteoarthritis , retinitis pigmentosa , retinitis pigmentosa 90 Idh3b Disease Progression , fundus dystrophy , Huntington's disease-like 1 , optic atrophy , pantothenate kinase-associated neurodegeneration , retinitis pigmentosa , retinitis pigmentosa 46 , Stomach Neoplasms Idh3g adrenoleukodystrophy , autistic disorder , autosomal hemophilia A , Barth syndrome , cerebral creatine deficiency syndrome 1 , Chromosome Xq28 Duplication Syndrome , congenital disorder of glycosylation Iy , dyskeratosis congenita , Emery-Dreifuss muscular dystrophy , factor VIII deficiency , favism , immunodeficiency 33 , paraplegia , periventricular nodular heterotopia , quadriplegia , severe congenital encephalopathy due to MECP2 mutation , Splenomegaly , syndromic X-linked intellectual disability Lubs type Mdh1 Acute Liver Failure , adult respiratory distress syndrome , Bardet-Biedl syndrome , Chemical and Drug Induced Liver Injury , developmental and epileptic encephalopathy 88 , Experimental Liver Cirrhosis , hypertension , Liver Injury Mdh2 Animal Mammary Neoplasms , brain disease , brain ischemia , carcinoma , Chromosome 7q11.23 Deletion Syndrome, Distal, 1.2-MB , congestive heart failure , developmental and epileptic encephalopathy 1 , developmental and epileptic encephalopathy 51 , Experimental Mammary Neoplasms , genetic disease , myocardial infarction , ovarian carcinoma , pleomorphic xanthoastrocytoma Mpc1 Fraser syndrome 3 , mitochondrial pyruvate carrier deficiency , substance-related disorder Ogdh Chemical and Drug Induced Liver Injury , oxoglutarate dehydrogenase deficiency , pleomorphic xanthoastrocytoma Ogdhl Cockayne syndrome B , congestive heart failure , depressive disorder , genetic disease , megacolon , schizophrenia , Yoon-Bellen neurodevelopmental syndrome Pc Aicardi-Goutieres Syndrome 3 , bipolar disorder , Burkitt lymphoma , Chemical and Drug Induced Liver Injury , Congenital Infantile Lactic Acidosis , Developmental Disabilities , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , genetic disease , immunodeficiency 90 , intellectual disability , Leigh Necrotizing Encephalopathy due to Pyruvate Carboxylase Deficiency , pyruvate carboxylase deficiency disease , type 2 diabetes mellitus Pck1 Alzheimer's disease , celiac disease , Chronic Intermittent Hypoxia , congestive heart failure , Endotoxemia , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Fetal Growth Retardation , genetic disease , hepatocellular carcinoma , hyperglycemia , metabolic dysfunction-associated steatohepatitis , Metabolic Syndrome , obesity , Phosphoenolpyruvate Carboxykinase Deficiency , Phosphoenolpyruvate Carboxykinase Deficiency, Cytosolic , type 2 diabetes mellitus Pck2 Brain-Lung-Thyroid Syndrome , COVID-19 , Endotoxemia , Experimental Liver Cirrhosis , Hypoxia , lysinuric protein intolerance , Phosphoenolpyruvate Carboxykinase Deficiency , Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial , retinitis pigmentosa 27 , Specific Granule Deficiency Pdha1 autistic disorder , Coffin-Lowry syndrome , developmental and epileptic encephalopathy 2 , Disease Progression , epilepsy , genetic disease , glycogen storage disease IXA , lactic acidosis , Leigh Syndrome, X-Linked , mitochondrial metabolism disease , Myocardial Ischemia , Nance-Horan syndrome , Neurodevelopmental Disorders , osteoarthritis , Prostatic Neoplasms , pyruvate decarboxylase deficiency , Pyruvate Dehydrogenase E1 Alpha Deficiency , Pyruvate Metabolism, Inborn Errors , Stomach Neoplasms , sudden infant death syndrome , syndromic X-linked intellectual disability Lubs type Pdha2 azoospermia , spermatogenic failure 1 , spermatogenic failure 70 Pdhb epilepsy , genetic disease , pyruvate decarboxylase deficiency , Pyruvate Dehydrogenase E1-Beta Deficiency , Pyruvate Dehydrogenase Phosphatase Deficiency , renal cell carcinoma Sdha B-lymphoblastic leukemia/lymphoma with hypodiploidy , Brain Neoplasms , Breast Cancer, Familial , Carney Triad , diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype , dilated cardiomyopathy , dilated cardiomyopathy 1GG , dopamine transporter deficiency syndrome , gastrointestinal stromal tumor , Hereditary Neoplastic Syndromes , Hereditary Paraganglioma-Pheochromocytoma Syndromes , hereditary renal cell carcinoma , Infantile Polymyoclonus , interstitial lung disease 2 , Leigh disease , lung non-small cell carcinoma , mitochondrial complex II deficiency , Mitochondrial Complex II Deficiency Nuclear Type 1 , multiple endocrine neoplasia type 2A , muscular disease , myopathy , Neurodegeneration with Ataxia and Late-Onset Optic Atrophy , Opsoclonus-Myoclonus Syndrome , osteoarthritis , paraganglioma , Paragangliomas 1 , Paragangliomas 3 , Paragangliomas 4 , Paragangliomas 5 , Parkinson's disease , Peritoneal Adhesions , pheochromocytoma , pilocytic astrocytoma , Pulmonary Atresia , rhabdomyosarcoma , Subacute Necrotizing Encephalopathy of Leigh, Infantile Sdhb acute myocardial infarction , Bannayan-Riley-Ruvalcaba syndrome , bilateral breast cancer , breast cancer , Carney Triad , Carney-Stratakis syndrome , Carotid Body Tumor , chromosome 1p36 deletion syndrome , Cowden syndrome , gastrointestinal stromal tumor , Hereditary Neoplastic Syndromes , Hereditary Paraganglioma-Pheochromocytoma Syndromes , Islet Cell Tumor Syndrome , Kidney Neoplasms , mitochondrial complex II deficiency , Mitochondrial Complex II Deficiency Nuclear Type 1 , Mitochondrial Complex II Deficiency Nuclear Type 4 , Nijmegen breakage syndrome , ovarian cancer , paraganglioma , Paragangliomas 3 , Paragangliomas 4 , pheochromocytoma , renal cell carcinoma , Renal Cell Carcinoma 1 , type 2 diabetes mellitus , von Hippel-Lindau disease Sdhc autoimmune interstitial lung, joint, and kidney disease , breast cancer , Carney Triad , Carney-Stratakis syndrome , Charcot-Marie-Tooth disease , Charcot-Marie-Tooth disease dominant intermediate D , Charcot-Marie-Tooth disease intermediate type , Charcot-Marie-Tooth disease type 1 , Charcot-Marie-Tooth disease type 1B , Charcot-Marie-Tooth disease type 2I , Charcot-Marie-Tooth disease type 4E , congenital muscular dystrophy , Cowden syndrome , gastrointestinal stromal tumor , Hereditary Neoplastic Syndromes , Hereditary Paraganglioma-Pheochromocytoma Syndromes , Islet Cell Tumor Syndrome , Leigh disease , lung non-small cell carcinoma , neuroblastoma , ovarian cancer , paraganglioma , Paragangliomas 3 , parathyroid carcinoma , pheochromocytoma , rhabdomyosarcoma Sdhd ataxia telangiectasia , BH4-deficient hyperphenylalaninemia A , Carney-Stratakis syndrome , chromosome 11 partial duplication syndrome , combined oxidative phosphorylation deficiency 8 , COVID-19 , Cowden syndrome , dilated cardiomyopathy 1II , Glomus Jugulare Tumor , Hereditary Neoplastic Syndromes , Hereditary Paraganglioma-Pheochromocytoma Syndromes , intellectual disability , Intestinal Carcinoid Tumors , Islet Cell Tumor Syndrome , melanoma , microcephaly , mitochondrial complex II deficiency , Mitochondrial Complex II Deficiency Nuclear Type 1 , Mitochondrial Complex II Deficiency Nuclear Type 3 , paraganglioma , Paragangliomas 1 , Paragangliomas 3 , Paragangliomas 4 , Paragangliomas with Sensorineural Hearing Loss , pheochromocytoma , Pyruvate Dehydrogenase E2 Deficiency , renal cell carcinoma Sucla2 chromosome 13q14 deletion syndrome , Developmental Disabilities , genetic disease , intellectual disability , mitochondrial DNA depletion syndrome , mitochondrial DNA depletion syndrome 5 , obesity , retinoblastoma Suclg1 Disease Progression , genetic disease , mitochondrial DNA depletion syndrome , mitochondrial DNA depletion syndrome 9 , Stomach Neoplasms Suclg2 Animal Disease Models , endometriosis , lung adenocarcinoma , methylmalonic acidemia , mitochondrial DNA depletion syndrome 9 , obesity
2-hydroxyglutaric aciduria Idh2 acute intermittent porphyria Aco2 Acute Liver Failure Idh1 , Mdh1 acute lymphoblastic leukemia Idh1 acute myeloid leukemia Idh1 , Idh2 acute myocardial infarction Idh2 , Sdhb acute promyelocytic leukemia Idh1 , Idh2 adenoid cystic carcinoma Idh1 adenylosuccinase lyase deficiency Aco2 adrenoleukodystrophy Idh3g adult respiratory distress syndrome Aco2 , Mdh1 Aicardi-Goutieres Syndrome 3 Pc Alzheimer's disease Dlst , Pck1 Animal Disease Models Idh2 , Suclg2 Animal Mammary Neoplasms Mdh2 ataxia telangiectasia Dlat , Sdhd atrial fibrillation Cs autistic disorder Idh3g , Pdha1 autoimmune disease Idh1 autoimmune interstitial lung, joint, and kidney disease Sdhc autosomal hemophilia A Idh3g azoospermia Pdha2 B-lymphoblastic leukemia/lymphoma Fh B-lymphoblastic leukemia/lymphoma with hypodiploidy Sdha Bannayan-Riley-Ruvalcaba syndrome Sdhb Bardet-Biedl syndrome Mdh1 Barth syndrome Idh3g BH4-deficient hyperphenylalaninemia A Dlat , Sdhd bilateral breast cancer Sdhb bipolar disorder Cs , Pc Bloom syndrome Idh2 , Idh3a bone remodeling disease Idh2 brain disease Mdh2 Brain Hypoxia-Ischemia Cs brain ischemia Mdh2 Brain Neoplasms Idh1 , Sdha Brain-Lung-Thyroid Syndrome Pck2 breast cancer Fh , Sdhb , Sdhc Breast Cancer, Familial Sdha Breast Neoplasms Idh1 Burkitt lymphoma Pc carcinoma Mdh2 Cardiomegaly Cs , Idh2 cardiomyopathy Cs Carney Triad Sdha , Sdhb , Sdhc Carney-Stratakis syndrome Dlat , Sdhb , Sdhc , Sdhd Carotid Body Tumor Sdhb celiac disease Pck1 central nervous system disease Idh2 cerebral creatine deficiency syndrome 1 Idh3g Charcot-Marie-Tooth disease Sdhc Charcot-Marie-Tooth disease dominant intermediate D Sdhc Charcot-Marie-Tooth disease intermediate type Sdhc Charcot-Marie-Tooth disease type 1 Sdhc Charcot-Marie-Tooth disease type 1B Sdhc Charcot-Marie-Tooth disease type 2I Sdhc Charcot-Marie-Tooth disease type 4E Sdhc Chemical and Drug Induced Liver Injury Dlat , Idh2 , Mdh1 , Ogdh , Pc cholangiocarcinoma Idh1 , Idh2 Cholangiofibrosis Idh1 chondroma Idh1 , Idh2 chromosome 11 partial duplication syndrome Dlat , Sdhd chromosome 13q14 deletion syndrome Sucla2 chromosome 1p36 deletion syndrome Sdhb Chromosome 7q11.23 Deletion Syndrome, Distal, 1.2-MB Mdh2 Chromosome Xq28 Duplication Syndrome Idh3g Chronic Allograft Nephropathy Aco1 , Cs Chronic Cerebral Hypoperfusion Aco1 Chronic Intermittent Hypoxia Pck1 Cockayne syndrome B Ogdhl Coffin-Lowry syndrome Pdha1 colorectal cancer Idh2 , Idh3a combined oxidative phosphorylation deficiency 8 Sdhd common variable immunodeficiency 4 Aco2 congenital disorder of glycosylation Il Dlat congenital disorder of glycosylation Iy Idh3g Congenital Infantile Lactic Acidosis Pc Congenital Infantile Lactic Acidosis due to LAD Deficiency Dld congenital muscular dystrophy Sdhc congestive heart failure Acly , Cs , Mdh2 , Ogdhl , Pck1 COVID-19 Aco2 , Fh , Idh1 , Pck2 , Sdhd Cowden syndrome Sdhb , Sdhc , Sdhd Craniofacial Abnormalities Idh2 D-2-hydroxyglutaric aciduria Idh2 D-2-hydroxyglutaric aciduria 2 Idh2 depressive disorder Ogdhl developmental and epileptic encephalopathy 1 Mdh2 developmental and epileptic encephalopathy 2 Pdha1 developmental and epileptic encephalopathy 51 Mdh2 developmental and epileptic encephalopathy 88 Mdh1 Developmental Disabilities Aco2 , Pc , Sucla2 diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype Idh1 , Sdha dilated cardiomyopathy Cs , Sdha dilated cardiomyopathy 1GG Sdha dilated cardiomyopathy 1II Dlat , Sdhd Disease Progression Idh3b , Pdha1 , Suclg1 dopamine transporter deficiency syndrome Sdha duodenal ulcer Aco1 dyskeratosis congenita Idh3g Emery-Dreifuss muscular dystrophy Idh3g endometriosis Suclg2 Endotoxemia Cs , Pck1 , Pck2 epilepsy Pdha1 , Pdhb esophagus squamous cell carcinoma Idh2 Experimental Diabetes Mellitus Cs , Pc , Pck1 Experimental Liver Cirrhosis Mdh1 , Pc , Pck1 , Pck2 Experimental Mammary Neoplasms Mdh2 factor VIII deficiency Idh3g favism Idh3g Fetal Growth Retardation Pck1 Fraser syndrome 3 Mpc1 fumarase deficiency Fh fundus dystrophy Aco2 , Idh3a , Idh3b gastrointestinal stromal tumor Fh , Sdha , Sdhb , Sdhc genetic disease Aco2 , Dlat , Dld , Idh2 , Mdh2 , Ogdhl , Pc , Pck1 , Pdha1 , Pdhb , Sucla2 , Suclg1 glioblastoma Idh1 Glomus Jugulare Tumor Sdhd glycogen storage disease IXA Pdha1 Growth Disorders Idh2 hemangioma Idh1 , Idh2 hepatoblastoma Fh hepatocellular carcinoma Acly , Aco2 , Fh , Idh1 , Idh2 , Pck1 hepatocellular clear cell carcinoma Idh1 , Idh2 Hereditary Leiomyomatosis and Renal Cell Cancer Fh Hereditary Neoplastic Syndromes Fh , Sdha , Sdhb , Sdhc , Sdhd Hereditary Paraganglioma-Pheochromocytoma Syndromes Dlst , Sdha , Sdhb , Sdhc , Sdhd hereditary renal cell carcinoma Sdha high grade glioma Idh1 Huntington's disease-like 1 Idh3b hydronephrosis Idh2 hyperglycemia Pck1 hypertension Mdh1 hyperthyroidism Cs hypertrophic cardiomyopathy Cs , Idh2 hypothyroidism Cs Hypoxia Cs , Pck2 Immunoblastic Lymphadenopathy Idh2 immunodeficiency 33 Idh3g immunodeficiency 90 Pc infantile cerebellar-retinal degeneration Aco2 Infantile Polymyoclonus Sdha intellectual disability Dlat , Dlst , Pc , Sdhd , Sucla2 interstitial lung disease 2 Sdha Intestinal Carcinoid Tumors Sdhd intrahepatic cholangiocarcinoma Idh1 , Idh2 Islet Cell Tumor Syndrome Sdhb , Sdhc , Sdhd kidney failure Idh2 Kidney Neoplasms Sdhb lactic acidosis Dld , Pdha1 Leigh disease Dlat , Dld , Sdha , Sdhc Leigh Necrotizing Encephalopathy due to Pyruvate Carboxylase Deficiency Pc Leigh Syndrome, X-Linked Pdha1 leiomyoma cutis Fh limb ischemia Cs lissencephaly 5 Dld Liver Injury Mdh1 Liver Reperfusion Injury Cs , Idh2 lung adenocarcinoma Idh1 , Idh2 , Suclg2 lung cancer Idh2 lung non-small cell carcinoma Fh , Idh2 , Sdha , Sdhc lung squamous cell carcinoma Idh1 , Idh2 lymphoma Idh1 lysinuric protein intolerance Pck2 Maffucci syndrome Idh1 , Idh2 maple syrup urine disease Dld megacolon Ogdhl Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 Fh melanoma Sdhd metabolic dysfunction-associated steatohepatitis Idh2 , Pck1 metabolic dysfunction-associated steatotic liver disease Aco1 , Idh2 Metabolic Syndrome Idh2 , Pck1 methylmalonic acidemia Suclg2 microcephaly Fh , Sdhd mitochondrial complex II deficiency Sdha , Sdhb , Sdhd Mitochondrial Complex II Deficiency Nuclear Type 1 Sdha , Sdhb , Sdhd Mitochondrial Complex II Deficiency Nuclear Type 3 Sdhd Mitochondrial Complex II Deficiency Nuclear Type 4 Sdhb mitochondrial DNA depletion syndrome Sucla2 , Suclg1 mitochondrial DNA depletion syndrome 5 Sucla2 mitochondrial DNA depletion syndrome 9 Suclg1 , Suclg2 mitochondrial metabolism disease Aco2 , Idh2 , Pdha1 mitochondrial pyruvate carrier deficiency Mpc1 multiple endocrine neoplasia type 2A Sdha muscular disease Sdha myelodysplastic syndrome Idh1 , Idh2 myocardial infarction Cs , Mdh2 Myocardial Ischemia Dlat , Pdha1 myopathy Sdha Nance-Horan syndrome Pdha1 Neoplasm Invasiveness Aco1 Neoplasm Recurrence, Local Idh1 , Idh2 neuroblastoma Sdhc Neurodegeneration with Ataxia and Late-Onset Optic Atrophy Sdha Neurodevelopmental Disorders Fh , Idh1 , Pdha1 Nijmegen breakage syndrome Sdhb obesity Acly , Cs , Idh1 , Pck1 , Sucla2 , Suclg2 oligodendroglioma Idh1 , Idh2 Ollier disease Idh1 , Idh2 Opsoclonus-Myoclonus Syndrome Sdha optic atrophy Aco2 , Idh3b optic atrophy 9 Aco2 osteoarthritis Aco1 , Idh2 , Idh3a , Pdha1 , Sdha osteoporosis Idh2 ovarian cancer Fh , Sdhb , Sdhc ovarian carcinoma Mdh2 oxoglutarate dehydrogenase deficiency Dlst , Ogdh pantothenate kinase-associated neurodegeneration Idh3b paraganglioma Dlst , Sdha , Sdhb , Sdhc , Sdhd Paragangliomas 1 Sdha , Sdhd Paragangliomas 3 Sdha , Sdhb , Sdhc , Sdhd Paragangliomas 4 Sdha , Sdhb , Sdhd Paragangliomas 5 Sdha Paragangliomas 7 Dlst Paragangliomas with Sensorineural Hearing Loss Sdhd paraplegia Idh3g parathyroid carcinoma Fh , Sdhc Parkinson's disease Sdha paroxysmal extreme pain disorder Idh1 peripheral T-cell lymphoma Idh2 Peritoneal Adhesions Sdha periventricular nodular heterotopia Idh3g pheochromocytoma Sdha , Sdhb , Sdhc , Sdhd Phosphoenolpyruvate Carboxykinase Deficiency Pck1 , Pck2 Phosphoenolpyruvate Carboxykinase Deficiency, Cytosolic Pck1 Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial Pck2 pilocytic astrocytoma Sdha pleomorphic xanthoastrocytoma Dld , Mdh2 , Ogdh primary pulmonary hypertension Idh1 prostate adenocarcinoma Idh1 prostate cancer Dlat Prostatic Neoplasms Idh1 , Pdha1 Pulmonary Atresia Sdha pyruvate carboxylase deficiency disease Pc pyruvate decarboxylase deficiency Dld , Pdha1 , Pdhb Pyruvate Dehydrogenase E1 Alpha Deficiency Pdha1 Pyruvate Dehydrogenase E1-Beta Deficiency Pdhb Pyruvate Dehydrogenase E2 Deficiency Dlat , Sdhd Pyruvate Dehydrogenase Phosphatase Deficiency Pdhb Pyruvate Metabolism, Inborn Errors Pdha1 quadriplegia Idh3g renal cell carcinoma Fh , Pdhb , Sdhb , Sdhd Renal Cell Carcinoma 1 Sdhb retinitis pigmentosa Idh3a , Idh3b retinitis pigmentosa 27 Pck2 retinitis pigmentosa 46 Idh3b retinitis pigmentosa 90 Idh3a retinoblastoma Sucla2 rhabdomyosarcoma Sdha , Sdhc Rubinstein-Taybi syndrome Aco2 schizophrenia Ogdhl Sepsis Cs severe congenital encephalopathy due to MECP2 mutation Idh3g skin melanoma Idh1 Sleep Deprivation Dlat Specific Granule Deficiency Pck2 spermatogenic failure 1 Pdha2 spermatogenic failure 70 Pdha2 spinocerebellar ataxia 45 Fh Splenomegaly Idh3g status epilepticus Idh2 stomach cancer Idh2 Stomach Neoplasms Idh3b , Pdha1 , Suclg1 Subacute Necrotizing Encephalopathy of Leigh, Infantile Dld , Sdha substance-related disorder Mpc1 sudden infant death syndrome Pdha1 syndromic X-linked intellectual disability Lubs type Idh3g , Pdha1 teratoma Idh2 type 2 diabetes mellitus Pc , Pck1 , Sdhb uterine fibroid Fh Vascular Malformations Idh2 Ventricular Dysfunction, Left Cs , Idh2 von Hippel-Lindau disease Sdhb Yoon-Bellen neurodevelopmental syndrome Ogdhl
