Krebs cycle disorders (Homo sapiens)

From WikiPathways

Revision as of 17:40, 25 April 2019 by IreneHemel (Talk | contribs)
Jump to: navigation, search
31, 2, 42, 42, 4Complex formation of SCS with NDPK is inprotant for deoxyribonucleotide salvation, which is needed for mtDNA synthesis and integrity.Relevant metabolic pathways,illustrating the metabolic effects of succinyl-CoA sythethase deficiencymtDNA synthesisSUCLA2NDPKADP-forming (A-SCS)2-oxoglutaric aciduriaIn most patient, E2 subunit seems responsible for "classic metabolic" presentation of diseaseEncephalopathic form is related to E2 subunit deficiencyalpha-ketoglutarateFumarateE1-subunitGDP-forming(G-SCS)FH2-KGD complexOxaloacetateMethylmalonyl-CoA(S)-malatepyruvatelactateSuccinyl coenzyme AAcetyl-CoAADPpropionylATPMETHYLMALONIC ACIDGTPcitratesuccinatemethylcitrateMETHYLMALONYL CARNITINE ESTER (C4DC)SUCCINYL CARNITINEESTER (C4DC)3-HYDROXYPROPIONATEPROPIONYLCARNITINE (C3)E2-subunitE3-subunit2-oxoglutaric aciduria:encephalopathic form2-oxoglutaric aciduria:'DOOR syndrome"Clinically recognisable form of:deafness, onycho-osteodystrophy,thumbs and sensorineural deafness,is related to defect of E1 subunit.Fumarase deficiencySCS deficiencySUCLA2SCS deficiencySUCLG1SUCLG1SUCLG2GDPSUCLG1GDP-forming(G-SCS)SUCLG1SUCLG2SUCLA2ADP-forming (A-SCS)SUCLG1GDP-forming(G-SCS)SUCLG1SUCLG2NDPKSUCLA2ADP-forming (A-SCS)SUCLG1NDPK1, 2, 41, 2, 42, 4


Description

This pathway shows an simplified version of the Krebs cycle (for more details see [1] ), with 4 genetic diseases related to it.

For succinyl-CoA synthetase deficiencies, relevant metabolic markers are depicted in light green. Patients with a mutation in the SUCLG1 might present a severe (fatal) form of mitochondrial encephalomyopathy.

This pathway was inspired by Chapter 20 of the book of Blau (ISBN 3642403360 (978-3642403361)).

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Kyle S McCommis, Brian N Finck; ''Mitochondrial pyruvate transport: a historical perspective and future research directions ''; Biochem J., 2015 PubMed Europe PMC Scholia
  2. Kowluru A, Tannous M, Chen HQ; ''Localization and characterization of the mitochondrial isoform of the nucleoside diphosphate kinase in the pancreatic beta cell: evidence for its complexation with mitochondrial succinyl-CoA synthetase.''; Arch Biochem Biophys, 2002 PubMed Europe PMC Scholia
  3. Kavanaugh-Black A, Connolly DM, Chugani SA, Chakrabarty AM; ''Characterization of nucleoside-diphosphate kinase from Pseudomonas aeruginosa: complex formation with succinyl-CoA synthetase.''; Proc Natl Acad Sci U S A, 1994 PubMed Europe PMC Scholia
  4. Lawrence R Gray, Sean C Tompkins, Eric B Taylor; ''Disorders of the Pyruvate Metabolism and the Krebs Cycle''; Cell Mol Life Sci ., 2014 PubMed Europe PMC Scholia
  5. Kadrmas EF, Ray PD, Lambeth DO; ''Apparent ATP-linked succinate thiokinase activity and its relation to nucleoside diphosphate kinase in mitochondrial matrix preparations from rabbit.''; Biochim Biophys Acta, 1991 PubMed Europe PMC Scholia
  6. Nenad Blau, Marinus Duran, K Michael Gibson, Carlo Dionisi-Vici.; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; Springer-Verlag Berlin Heidelberg, 2014

History

View all...
CompareRevisionActionTimeUserComment
128282view01:21, 30 January 2024EweitzFix legend layout
128281view01:18, 30 January 2024EweitzCopyedit nodes, standardize case
128280view01:08, 30 January 2024EweitzSoften disease color
123795view15:24, 12 August 2022DeSlAdded some more proteins, and cytosol vs mitochondrial matrix location
123794view15:18, 12 August 2022DeSlConvert arrow to translocation
123793view15:16, 12 August 2022DeSlAdded pyruvate transport
123792view15:11, 12 August 2022DeSlAdded reaction to Alanine
123791view15:05, 12 August 2022DeSlAdded LDH tetramers
123790view14:50, 12 August 2022DeSlAdded another lit. ref to full PW
123789view14:45, 12 August 2022DeSlAdding ID for Succinyl carnitine ester
120410view09:27, 30 November 2021Fehrhartboxed pathway node
119280view10:43, 23 June 2021FinterlyAdded ISBN for book citation
117701view12:21, 22 May 2021EweitzModified title
107304view14:36, 19 September 2019EgonwRemove an empty ChEBI identifier
107163view14:25, 17 September 2019MaintBotChEBI identifier normalization
106785view13:26, 17 September 2019MaintBotHMDB identifier normalization
104644view07:31, 7 June 2019JosienlandmanConverted the interaction lines to the diseases into graphical lines
104027view17:40, 25 April 2019IreneHemelModified description
102830view15:59, 24 January 2019DeSlModified description
102829view15:58, 24 January 2019DeSlAnnotated nodes.
102715view13:26, 21 January 2019DeSlModified description
98924view05:20, 16 October 2018EgonwModified description
98275view15:29, 15 August 2018DeSlModified description
98274view15:27, 15 August 2018DeSlModified description
98273view15:24, 15 August 2018DeSlOntology Term : 'mitochondrial encephalomyopathy' added !
98272view15:23, 15 August 2018DeSlChanged some MIM-conversion to arrows, since it's not sure if there is a one step conversion proccess involved.
98271view15:22, 15 August 2018DeSlAdded info on boxed metabolites.
98270view15:19, 15 August 2018DeSlAdded last unconnected line
98269view15:06, 15 August 2018DeSlAdded more info on SCS protein complex
98268view14:54, 15 August 2018DeSlAdded specific subunits of SCS complex
98267view14:17, 15 August 2018DeSlOntology Term : 'methylmalonic acidemia' added !
98266view14:15, 15 August 2018DeSlOntology Term : 'fumaric aciduria pathway' added !
98265view14:15, 15 August 2018DeSlOntology Term : 'citric acid cycle pathway' added !
98264view14:14, 15 August 2018DeSlModified description
98263view14:13, 15 August 2018DeSlAdded diseases as text boxes (with OMIM linkouts), changed layout, added some enzymes+metabolites to close the cycle.
96740view05:58, 2 April 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96739view05:57, 2 April 2018EgonwRemoved a wrong identifier
96576view13:54, 21 March 2018Richard97New pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(S)-malateMetaboliteQ27104150 (Wikidata) Not in original drawing, adapted from https://www.wikipathways.org/index.php/Pathway:WP78
2-KGD complexProteinQ1B4V6 (Uniprot-TrEMBL)
  • Composed of 3 subunits
  • "Homodimer. The 2-oxoglutarate dehydrogenase (ODH) complex contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) (By similarity)." [https://www.uniprot.org/uniprot/Q1B4V6]
3-HYDROXYPROPIONATEMetaboliteQ27101949 (Wikidata)
ADP-forming (A-SCS)Protein6.2.1.5 (Enzyme Nomenclature)
  • SCS (succinyl-CoA syntethase)
  • For more info see: https://en.wikipedia.org/wiki/Succinyl_coenzyme_A_synthetase
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Acetyl-CoAMetaboliteQ715317 (Wikidata)
E1-subunitProteinQ96HY7 (Uniprot-TrEMBL)
E2-subunitProteinP36957 (Uniprot-TrEMBL)
E3-subunitProteinO00330 (Uniprot-TrEMBL)
FHGeneProduct2271 (Entrez Gene) Fumarate hydratase
FumarateMetaboliteCHEBI:18012 (ChEBI)
GDP-forming(G-SCS)Protein6.2.1.4 (Enzyme Nomenclature)
  • SCS (succinyl-CoA syntethase)
  • For more info see: https://en.wikipedia.org/wiki/Succinyl_coenzyme_A_synthetase
GDPMetaboliteCHEBI:17552 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
METHYLMALONIC ACIDMetaboliteCHEBI:30860 (ChEBI)
METHYLMALONYL CARNITINE ESTER (C4DC)MetaboliteHMDB0062785 (HMDB)
Methylmalonyl-CoAMetaboliteHMDB01269 (HMDB)
NDPKProtein2.7.4.6 (Enzyme Nomenclature) Nucleoside diphosphate kinase
OxaloacetateMetaboliteQ408658 (Wikidata) Not in original drawing, adapted from https://www.wikipathways.org/index.php/Pathway:WP78
PROPIONYLCARNITINE (C3)MetaboliteQ27103933 (Wikidata) a.k.a. 2-methylcitric acid
SUCCINYL CARNITINE ESTER (C4DC)Metabolite
SUCLA2ProteinQ9P2R7 (Uniprot-TrEMBL)
SUCLG1ProteinP53597 (Uniprot-TrEMBL)
SUCLG2ProteinQ96I99 (Uniprot-TrEMBL)
Succinyl coenzyme AMetaboliteCHEBI:15380 (ChEBI)
alpha-ketoglutarateMetaboliteCHEBI:16810 (ChEBI)
citrateMetaboliteCHEBI:133748 (ChEBI)
lactateMetaboliteCHEBI:24996 (ChEBI)
methylcitrateMetaboliteQ27104155 (Wikidata) a.k.a. 2-methylcitric acid
mtDNA synthesisPathwayWP111 (WikiPathways)
propionylMetaboliteCHEBI:26294 (ChEBI)
pyruvateMetaboliteCHEBI:15361 (ChEBI)
succinateMetaboliteCHEBI:30031 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4236"
Personal tools