Riboflavin and CoQ disorders (Homo sapiens)

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mitochondria733 CytosolBVVLS1APTXAMPOne carbonmetabolismPyrimidine metabolismand related disordersCETFPDSS1FADH2trans-decaprenyl-PPOXPHOS6 IPPCoQ10a ubiquinoneFMNCABC1ETFDH geneETFDH6 PPFarnesyl-PPRiboflavin kinaseFAD synthetaseMevalonatepathway8, 12310, 161, 2, 4, 9, 11...RIBSLC52A1FMNRIBFAD3SLC52A2SLC52A3BVVLS2Fazio-LondeSyndromeRiboflavin DeficiencyDiseaseCatalysisPathwayStimulationProteinMetaboliteConversionConnection to diseaseLegendETFAETFBMADDFAD3a ubiquinolFADFADPHBDHBall-E-10PrP2COQ25PPiCoQ2 deficiency 55FAD COQ6 DHDBCoQ6 deficiency Q10H2DMQ10H2DeMQ10H2MHDBDMPhOHMDMQ10H2COQ7 Fe2+ COQ9 CoQ9 deficiency PDSS2trans-nonaprenyl-PP7 PP7 IPPPDSS1 deficiency PDSS2 deficiency CABC1/ADCK3 deficiency 1212Ataxia oculomotorApraxia 1 (AOA1)10, 1610, 16


Description

Riboflavin (aka Vitamin B2) is used as molecular precursor for the formation of FAD and FMN, which are both essential cofactors in beta-oxidation, branched-chain-amino-acid catabolism and the mitochondrial electron transport of the TCA cycle.

Coenzyme Q10 (aka ubiquinone or CoQ10) functions as a electron carrier, antioxidant and influences pyrimidine metabolism directly.

This pathway was inspired by Chapter 16 (ed. 4) from the book of Blau (ISBN 3642403360 (978-3642403361)).

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Ontology Terms

 

Bibliography

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  1. Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR.; ''Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment.''; PubMed Europe PMC Scholia
  2. Yao Y, Yonezawa A, Yoshimatsu H, Masuda S, Katsura T, Inui K.; ''Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain.''; PubMed Europe PMC Scholia
  3. Barile M, Giancaspero TA, Brizio C, Panebianco C, Indiveri C, Galluccio M, Vergani L, Eberini I, Gianazza E; ''Biosynthesis of flavin cofactors in man: implications in health and disease.''; Curr Pharm Des, 2013 PubMed Europe PMC Scholia
  4. Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR; ''Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment.''; J Inherit Metab Dis, 2011 PubMed Europe PMC Scholia
  5. Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, Dimauro S, Hirano M; ''A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency.''; Am J Hum Genet, 2006 PubMed Europe PMC Scholia
  6. Tekle M, Turunen M, Dallner G, Chojnacki T, Swiezewska E.; ''Investigation of coenzyme Q biosynthesis in human fibroblast and HepG2 cells.''; PubMed Europe PMC Scholia
  7. Nenad Blau, Carlo Dionisi Vici, K Michael Gibson, Marinus Duran; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; Springer (ISBN-13: 978-3642403361), 2014
  8. Stefely JA, Reidenbach AG, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, Saunders JM, Johnson IE, Minogue CE, Wrobel RL, Barber GE, Lee D, Li S, Kannan N, Coon JJ, Bingman CA, Pagliarini DJ; ''Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis.''; Mol Cell, 2015 PubMed Europe PMC Scholia
  9. Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin JP, Raymond FL, Childs AM, Sheridan E, Edwards S, Josifova DJ; ''Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54.''; Am J Hum Genet, 2010 PubMed Europe PMC Scholia
  10. Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M; ''Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation.''; Neurology, 2005 PubMed Europe PMC Scholia
  11. Yonezawa A, Masuda S, Katsura T, Inui K.; ''Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1.''; PubMed Europe PMC Scholia
  12. Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A; ''CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures.''; Am J Hum Genet, 2008 PubMed Europe PMC Scholia
  13. Yoshimatsu H, Yonezawa A, Yao Y, Sugano K, Nakagawa S, Omura T, Matsubara K.; ''Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption.''; PubMed Europe PMC Scholia
  14. Forsgren M, Attersand A, Lake S, Grünler J, Swiezewska E, Dallner G, Climent I.; ''Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ.''; PubMed Europe PMC Scholia
  15. Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin JP, Raymond FL, Childs AM, Sheridan E, Edwards S, Josifova DJ.; ''Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54.''; PubMed Europe PMC Scholia
  16. Le Ber I, Dubourg O, Benoist JF, Jardel C, Mochel F, Koenig M, Brice A, Lombès A, Dürr A; ''Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1.''; Neurology, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114379view21:52, 8 January 2021DeSlOntology Term : 'ubiquinone biosynthetic pathway' added !
114378view21:52, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 6' added !
114377view21:51, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 5' added !
114376view21:51, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 4' added !
114375view21:51, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 3' added !
114374view21:51, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 2' added !
114373view21:49, 8 January 2021DeSlAdded another litref for APTX disorder
114372view21:47, 8 January 2021DeSlAdded lit. refs for CoQ2 and APTX related disorders
114371view21:45, 8 January 2021DeSlAdded APTX info and OXPHOS PW link.
114370view21:37, 8 January 2021DeSlAdded lit. ref. for CABC1 disorder
114369view21:35, 8 January 2021DeSlAdded CABC1 info
114368view21:25, 8 January 2021DeSlAdded PDSS1 and 2 info
114367view21:02, 8 January 2021DeSlAdded CoQ10 link to PW
114366view21:00, 8 January 2021DeSlAdded link to PW
114365view20:59, 8 January 2021DeSlConnected ubiquinol to CoQ10
114364view20:56, 8 January 2021DeSlAdded CoQ6 and 9
114363view20:40, 8 January 2021DeSlAdded COQ2 details
114362view20:26, 8 January 2021DeSlAdded details on ETFA and B
114361view19:53, 8 January 2021DeSlAdded more details on ETFDH
114354view15:35, 8 January 2021DeSlRemoved reactome IDs from interactions.
114353view15:33, 8 January 2021DeSlRemoved comment from Reactome on RIB translocation.
114352view15:32, 8 January 2021DeSlOntology Term : 'Brown-Vialetto-Van Laere syndrome 2' added !
114351view15:32, 8 January 2021DeSlOntology Term : 'Brown-Vialetto-Van Laere syndrome 1' added !
114350view15:31, 8 January 2021DeSlOntology Term : 'Brown-Vialetto-Van Laere syndrome' added !
114349view15:31, 8 January 2021DeSlOntology Term : 'coenzyme Q10 deficiency disease' added !
114348view15:31, 8 January 2021DeSlOntology Term : 'primary coenzyme Q10 deficiency 1' added !
114347view15:31, 8 January 2021DeSlOntology Term : 'riboflavin metabolic pathway' added !
114346view15:31, 8 January 2021DeSlOntology Term : 'riboflavin deficiency' added !
114345view15:30, 8 January 2021DeSlOntology Term : 'Fazio-Londe disease' added !
114344view15:30, 8 January 2021DeSlUpdate visualisation of cytosol
114343view15:27, 8 January 2021DeSlAdded reactions from RIB to FMN and FAD
114341view14:55, 8 January 2021DeSlUpdate description with chapter number
114340view14:54, 8 January 2021DeSlAdded legend
114339view14:43, 8 January 2021DeSlAdded link to pyrimidine PW
114337view14:27, 8 January 2021DeSlUpdate description
114336view14:23, 8 January 2021DeSlNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
6 IPPMetaboliteCHEBI:128769 (ChEBI) aka isopentenyl diphosphate
6 PPMetaboliteCHEBI:33019 (ChEBI) diphosphate
7 IPPMetaboliteCHEBI:128769 (ChEBI) aka isopentenyl diphosphate
7 PPMetaboliteCHEBI:33019 (ChEBI) diphosphate
AMPMetaboliteCHEBI:16027 (ChEBI) cofactor [https://en.wikipedia.org/wiki/Electron-transferring_flavoprotein]
APTXProteinQ7Z2E3 (Uniprot-TrEMBL)
CABC1ProteinQ8NI60 (Uniprot-TrEMBL)
  • aka COQ8A, ADCK3.
  • atypical kinase, substrate specificity unknown [https://www.uniprot.org/uniprot/Q8NI60]
CETFGeneProductIPR014730 (InterPro) aka electron transfer flavoprotein complex
COQ2ProteinQ96H96 (Uniprot-TrEMBL)
COQ6 ProteinQ9Y2Z9 (Uniprot-TrEMBL)
COQ7 ProteinQ99807 (Uniprot-TrEMBL)
COQ9 ProteinO75208 (Uniprot-TrEMBL)
CoQ10MetaboliteCHEBI:46245 (ChEBI)
DHBMetaboliteCHEBI:64136 (ChEBI)
DHDBMetaboliteCHEBI:50775 (ChEBI)
DMPhOHMetaboliteCHEBI:50774 (ChEBI)
DMQ10H2MetaboliteCHEBI:64181 (ChEBI)
DeMQ10H2MetaboliteCHEBI:64182 (ChEBI)
ETFAProteinP13804 (Uniprot-TrEMBL)
ETFBProtein38117 (Uniprot-TrEMBL)
ETFDH geneGeneProductENSG00000171503 (Ensembl)
ETFDHProteinQ16134 (Uniprot-TrEMBL)
FAD synthetaseProteinQ8NFF5 (Uniprot-TrEMBL) aka FLAD1, EC 2.7.7.2 [https://en.wikipedia.org/wiki/FMN_adenylyltransferase]
FAD MetaboliteCHEBI:16238 (ChEBI)
FADMetaboliteCHEBI:16238 (ChEBI)
FADMetaboliteCHEBI:57692 (ChEBI)
  • aka flavin adenine dinucleotide
  • cofactor [https://en.wikipedia.org/wiki/Electron-transferring_flavoprotein]
FADH2MetaboliteCHEBI:58307 (ChEBI)
FMNMetaboliteCHEBI:17621 (ChEBI)
FMNMetaboliteCHEBI:58210 (ChEBI) aka flavin mononucleotide
Farnesyl-PPMetaboliteCHEBI:175763 (ChEBI) aka Farnesyl PyroPhosphate
Fe2+ MetaboliteCHEBI:29033 (ChEBI)
MDMQ10H2MetaboliteCHEBI:64180 (ChEBI)
MHDBMetaboliteCHEBI:50776 (ChEBI)
Mevalonate pathwayPathwayWP3963 (WikiPathways)
OXPHOSPathwayWP111 (WikiPathways)
One carbon metabolismPathwayWP241 (WikiPathways)
PDSS1ProteinQ5T2R2 (Uniprot-TrEMBL)
PDSS2ProteinQ86YH6 (Uniprot-TrEMBL)
PHBMetaboliteCHEBI:30763 (ChEBI)
PPiMetaboliteCHEBI:29888 (ChEBI)
Pyrimidine metabolism and related disordersPathwayWP4225 (WikiPathways)
Q10H2MetaboliteCHEBI:64183 (ChEBI) aka ubiquinol-10
RIBMetaboliteCHEBI:17015 (ChEBI) aka riboflavin
Riboflavin kinaseProteinQ969G6 (Uniprot-TrEMBL) EC: 2.7.1.26 (according to Rhea)
SLC52A1ProteinQ9NWF4 (Uniprot-TrEMBL)
SLC52A2ProteinQ9HAB3 (Uniprot-TrEMBL)
SLC52A3ProteinSLC52A3 (Uniprot-TrEMBL)
a ubiquinolMetaboliteCHEBI:17976 (ChEBI)
a ubiquinoneMetaboliteCHEBI:16389 (ChEBI)
all-E-10PrP2MetaboliteCHEBI:61011 (ChEBI)
trans-deca prenyl-PPMetaboliteCHEBI:60721 (ChEBI) aka all-trans-decaprenyl diphosphate
trans-nona prenyl-PPMetaboliteCHEBI:58391 (ChEBI) aka all-trans-nonaprenyl diphosphate

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
6 IPPmim-conversion27803 (Rhea)
6 PPmim-conversion27803 (Rhea)
7 IPPmim-conversion55365 (Rhea)
7 PPmim-conversion55365 (Rhea)
DHBDHDBmim-conversion20362 (Rhea)
FADH2mim-conversion24052 (Rhea)
FADmim-conversion24052 (Rhea)
FMNFADmim-conversion17238 (Rhea)
Farnesyl-PPtrans-deca prenyl-PPmim-conversion27803 (Rhea)
Farnesyl-PPtrans-nona prenyl-PPmim-conversion55365 (Rhea)
Q10H2CoQ10Arrow61980 (Rhea)
RIBFMNmim-conversion14358 (Rhea)
RIBRIBmim-translocation35017 (Rhea)
a ubiquinonea ubiquinolmim-conversion24052 (Rhea)
all-E-10PrP2DHBmim-conversion44565 (Rhea)
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