Riboflavin and CoQ disorders (WP5037)

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)).
last edited

Authors

DeSl, Egonw, Finterly, and Fehrhart

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Rare Diseases

Annotations

Disease Ontology: primary coenzyme Q10 deficiency 2 Brown-Vialetto-Van Laere syndrome Fazio-Londe disease primary coenzyme Q10 deficiency 3 primary coenzyme Q10 deficiency 1 coenzyme Q10 deficiency disease primary coenzyme Q10 deficiency 4 riboflavin deficiency Brown-Vialetto-Van Laere syndrome 2 primary coenzyme Q10 deficiency 6 primary coenzyme Q10 deficiency 5 Brown-Vialetto-Van Laere syndrome 1

Pathway Ontology: riboflavin metabolic pathway ubiquinone biosynthetic pathway

Participants

Label Type Compact Identifier
One carbonmetabolism Pathway wikipathways:WP241
a ubiquinone Metabolite chebi:16389
Mevalonatepathway Pathway wikipathways:WP3963
PDSS1 Protein uniprot:Q5T2R2
Riboflavin kinase Protein uniprot:Q969G6
Pyrimidine metabolismand related disorders Pathway wikipathways:WP4225
FADH2 Metabolite chebi:58307
CABC1 Protein uniprot:Q8NI60
6 PP Metabolite chebi:33019
OXPHOS Pathway wikipathways:WP111
FMN Metabolite chebi:58210
APTX Protein uniprot:Q7Z2E3
trans-decaprenyl-PP Metabolite chebi:60721
CETF GeneProduct interpro:IPR014730
FAD synthetase Protein uniprot:Q8NFF5
CoQ10 Metabolite chebi:46245
ETFDH gene GeneProduct ensembl:ENSG00000171503
6 IPP Metabolite chebi:128769
ETFDH Protein uniprot:Q16134
Farnesyl-PP Metabolite chebi:175763
AMP Metabolite chebi:16027
RIB Metabolite chebi:17015
SLC52A1 Protein uniprot:Q9NWF4
FMN Metabolite chebi:17621
RIB Metabolite chebi:17015
FAD Metabolite chebi:16238
SLC52A2 Protein uniprot:Q9HAB3
SLC52A3 Protein uniprot:SLC52A3
ETFA Protein uniprot:P13804
ETFB Protein uniprot:38117
FAD Metabolite chebi:57692
a ubiquinol Metabolite chebi:17976
FAD Metabolite chebi:57692
FAD Metabolite chebi:57692
PHB Metabolite chebi:30763
DHB Metabolite chebi:64136
all-E-10PrP2 Metabolite chebi:61011
COQ2 Protein uniprot:Q96H96
PPi Metabolite chebi:29888
FAD Metabolite chebi:16238
COQ6 Protein uniprot:Q9Y2Z9
DHDB Metabolite chebi:50775
Q10H2 Metabolite chebi:64183
DMQ10H2 Metabolite chebi:64181
DeMQ10H2 Metabolite chebi:64182
MHDB Metabolite chebi:50776
DMPhOH Metabolite chebi:50774
MDMQ10H2 Metabolite chebi:64180
COQ7 Protein uniprot:Q99807
Fe2+ Metabolite chebi:29033
COQ9 Protein uniprot:O75208
PDSS2 Protein uniprot:Q86YH6
trans-nonaprenyl-PP Metabolite chebi:58391
7 PP Metabolite chebi:33019
7 IPP Metabolite chebi:128769

References

  1. Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, et al. Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology. 2005 Feb 8;64(3):539–41. PubMed Europe PMC Scholia
  2. Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, Dimauro S, et al. A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet. 2006 Feb;78(2):345–9. PubMed Europe PMC Scholia
  3. Le Ber I, Dubourg O, Benoist J-F, Jardel C, Mochel F, Koenig M, et al. Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1. Neurology. 2007 Jan 23;68(4):295–7. PubMed Europe PMC Scholia
  4. Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, et al. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet. 2008 Mar;82(3):623–30. PubMed Europe PMC Scholia
  5. Yonezawa A, Masuda S, Katsura T, Inui K. Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. Am J Physiol Cell Physiol. 2008 Sep;295(3):C632-41. PubMed Europe PMC Scholia
  6. Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin J-P, et al. Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. Am J Hum Genet. 2010 Mar 12;86(3):485–9. PubMed Europe PMC Scholia
  7. Yao Y, Yonezawa A, Yoshimatsu H, Masuda S, Katsura T, Inui K-I. Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. J Nutr. 2010 Jul;140(7):1220–6. PubMed Europe PMC Scholia
  8. Bosch AM, Abeling NGGM, Ijlst L, Knoester H, van der Pol WL, Stroomer AEM, et al. 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 Feb;34(1):159–64. PubMed Europe PMC Scholia
  9. Barile M, Giancaspero TA, Brizio C, Panebianco C, Indiveri C, Galluccio M, et al. Biosynthesis of flavin cofactors in man: implications in health and disease. Curr Pharm Des. 2013;19(14):2649–75. PubMed Europe PMC Scholia
  10. Yoshimatsu H, Yonezawa A, Yao Y, Sugano K, Nakagawa S, Omura T, et al. Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. Am J Physiol Gastrointest Liver Physiol. 2014 Jan;306(2):G102-10. PubMed Europe PMC Scholia
  11. Stefely JA, Reidenbach AG, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, et al. Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis. Mol Cell. 2015 Jan 8;57(1):83–94. PubMed Europe PMC Scholia
  12. PubMed Europe PMC Scholia