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Pathway Description
Betaine Drug Metabolism
Homo sapiens
Metabolic Pathway
Created: 2021-09-14
Last Updated: 2023-10-25
Betaine is obtained from foods such as wheat, shellfish, spinach, and beets. In the intestine, betaine is metabolized to trimethylamine (TMA) by the gut microbiota (Peptoclostridium acidaminophilum). The toxicity of betaine is due to the formation of TMA and its metabolism to Trimethylamine N-oxide (TMAO) in the liver. TMA is created from betaine via the enzyme betaine reductase in the intestinal microbe, then TMA then enters the bloodstream and is transported to the liver where dimethylaniline monooxygenase [N-oxide-forming] 3 converts TMA to TMAO. TMAO has negative effects on organs such as the heart, kidney and vascular system by contributing to cardiovascular disease, atherosclerosis, endothelial dysfunction and kidney disease.
References
Betaine Drug Metabolism References
Jameson E, Quareshy M, Chen Y: Methodological considerations for the identification of choline and carnitine-degrading bacteria in the gut. Methods. 2018 Oct 1;149:42-48. doi: 10.1016/j.ymeth.2018.03.012. Epub 2018 Apr 19.
Pubmed: 29684641
Rath, S., Rud, T., Pieper, D. H., & Vital, M. (2020). Potential tma-producing bacteria are ubiquitously found in mammalia. Frontiers in Microbiology, 10. https://doi.org/10.3389/fmicb.2019.02966
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Dolphin CT, Cullingford TE, Shephard EA, Smith RL, Phillips IR: Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FM04. Eur J Biochem. 1996 Feb 1;235(3):683-9. doi: 10.1111/j.1432-1033.1996.00683.x.
Pubmed: 8654418
Dolphin CT, Riley JH, Smith RL, Shephard EA, Phillips IR: Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA. Genomics. 1997 Dec 1;46(2):260-7. doi: 10.1006/geno.1997.5031.
Pubmed: 9417913
Yeung CK, Adman ET, Rettie AE: Functional characterization of genetic variants of human FMO3 associated with trimethylaminuria. Arch Biochem Biophys. 2007 Aug 15;464(2):251-9. doi: 10.1016/j.abb.2007.04.014. Epub 2007 May 2.
Pubmed: 17531949
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