Diet-dependent trimethylamine/trimethylamine N-oxide metabolism (Homo sapiens)

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7631, 244LiverLumen/GI TractProcess Mediated by Bacterial MetabolismR07228γBBFMO3DecarboxylationALDH7A1TMAO aldolaseTmmDimethylglycineTransmethylaseMalic SemialdehydeCholineBETALDSLC44A1CutC (and CutD)BETFADCaITCholineFADCHDHFADH2NADHH20BETCarnitine8TMACntA/B5, 6AcetateTMAOBetaine exporterBBU9, 109


Description

The host-microbiome pathway trimethylamine/trimethylamine N-oxide (TMA/TMAO) pathway which exists along the gut-heart axis. The precursors choline, l-carnitine and betaine are first microbially transformed to TMA. This metabolite is subsequently converted to TMAO by the flavin-containing monooxygenase 3.

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Ontology Terms

 

Bibliography

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  1. Craciun S, Balskus EP; ''Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme.''; Proc Natl Acad Sci U S A, 2012 PubMed Europe PMC Scholia
  2. Bodea S, Balskus EP; ''Purification and Characterization of the Choline Trimethylamine-Lyase (CutC)-Activating Protein CutD.''; Methods Enzymol, 2018 PubMed Europe PMC Scholia
  3. Zhao G, He F, Wu C, Li P, Li N, Deng J, Zhu G, Ren W, Peng Y; ''Betaine in Inflammation: Mechanistic Aspects and Applications.''; Front Immunol, 2018 PubMed Europe PMC Scholia
  4. Fennema D, Phillips IR, Shephard EA; ''Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease.''; Drug Metab Dispos, 2016 PubMed Europe PMC Scholia
  5. Gadda G; ''Choline oxidases.''; Enzymes, 2020 PubMed Europe PMC Scholia
  6. Buffa JA, Romano KA, Copeland MF, Cody DB, Zhu W, Galvez R, Fu X, Ward K, Ferrell M, Dai HJ, Skye S, Hu P, Li L, Parlov M, McMillan A, Wei X, Nemet I, Koeth RA, Li XS, Wang Z, Sangwan N, Hajjar AM, Dwidar M, Weeks TL, Bergeron N, Krauss RM, Tang WHW, Rey FE, DiDonato JA, Gogonea V, Gerberick GF, Garcia-Garcia JC, Hazen SL; ''The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism.''; Nat Microbiol, 2022 PubMed Europe PMC Scholia
  7. Wood AP, Warren FJ, Kelly DP; ''Methylotrophic Bacteria in Trimethylaminuria and Bacterial Vaginosis''; Springer Berlin Heidelberg, 2010 DOI Scholia
  8. Rajakovich LJ, Fu B, Bollenbach M, Balskus EP; ''Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria.''; Proc Natl Acad Sci U S A, 2021 PubMed Europe PMC Scholia
  9. Naumann E, Hippe H, Gottschalk G; ''Betaine: New Oxidant in the Stickland Reaction and Methanogenesis from Betaine and l-Alanine by a Clostridium sporogenes-Methanosarcina barkeri Coculture.''; Appl Environ Microbiol, 1983 PubMed Europe PMC Scholia
  10. Quareshy M, Shanmugam M, Townsend E, Jameson E, Bugg TDH, Cameron AD, Chen Y; ''Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition, and intersubunit electron transfer.''; J Biol Chem, 2021 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
126795view14:28, 22 June 2023DeSlConnected unconnected lines
126750view10:56, 18 June 2023EgonwAdded two more identifiers
126749view10:39, 18 June 2023EgonwFixed two references: removed duplicate Biopax tags, and added the DOI of a book.
125612view12:19, 4 March 2023EgonwUpdated the UniProt data sources
125098view00:39, 23 January 2023EweitzModified title
125094view11:08, 22 January 2023NvalenbrederAdded a clear visualization of which processes are mediated by bacterial metabolism, annotated nodes with standardized identifiers and added references to reactions
124176view18:02, 23 September 2022KhanspersOntology Term : 'classic metabolic pathway' added !
124171view08:51, 23 September 2022NvalenbrederChanged annotation of transmethylase enzyme
122739view13:08, 7 May 2022NvalenbrederFixed interactions and replaced cell compartment with mitochondria.
122409view09:37, 30 March 2022NvalenbrederModified title
122407view09:15, 30 March 2022NvalenbrederModified title
122397view20:22, 29 March 2022NvalenbrederModified title
122396view20:20, 29 March 2022NvalenbrederNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ALDH7A1ProteinENSG00000164904 (Ensembl)
AcetateMetaboliteC00033 (KEGG Compound)
BBUGeneProduct
BETALDMetaboliteC00576 (KEGG Compound)
BETMetaboliteC00719 (KEGG Compound)
Betaine exporter
CHDHProteinENSG00000016391 (Ensembl)
CaITGeneProduct
CarnitineMetaboliteC00318 (KEGG Compound)
CholineMetaboliteC00114 (KEGG Compound)
CntA/BProteinD0C9N6 (Uniprot-TrEMBL)
CutC (and CutD)GeneProduct
DecarboxylationPathway
DimethylglycineMetaboliteC01026 (KEGG Compound)
FADMetaboliteC00016 (KEGG Compound)
FADH2MetaboliteQ26998317 (Wikidata)
FMO3ProteinENSG00000007933 (Ensembl)
H20Metabolite15377 (ChEBI)
Malic SemialdehydePathwayQ119689804 (Wikidata)
NADHMetaboliteC00003 (KEGG Compound)
Process Mediated by Bacterial MetabolismPathway
R07228Pathway
SLC44A1ProteinENSG00000070214 (Ensembl)
TMAMetaboliteC00565 (KEGG Compound)
TMAO aldolaseProtein4.1.2.32 (KEGG Genes)
TMAOMetaboliteC01104 (KEGG Compound)
TmmProtein1.14.13.148 (KEGG Genes)
TransmethylaseGeneProductEC 2.1.1.157 (KEGG Genes)
γBBMetaboliteCHEMBL2074645 (ChEMBL compound)

Annotated Interactions

No annotated interactions

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