Flavin-containing monooxygenase 3

<h2 id="ligands">Ligands</h2>
List of human FMO3 substrates, inhibitors, inducers, and activators<table><tbody><tr><th>FMO3 <a href="/facts/Enzyme_substrate/6MnaV19h">substrates</a></th><th>FMO3 <a href="/facts/Enzyme_inhibitor/MkFwGXHJ">inhibitors</a></th><th>FMO3 <a href="/facts/Enzyme_inducer/k3S7bhdA">inducers</a></th><th>FMO3 <a href="/facts/Enzyme_activator/soAFcLGS">activators</a></th></tr><tr><td>Endogenous <a href="/facts/Biomolecule/DGvFzN7R">biomolecules</a><ul><li><a href="/facts/Epinephrine/k7vvMI7E">Epinephrine</a><a class="footnote-ref" id="fnref:25" href="#fn:25">25</a></li><li><a href="/facts/Norepinephrine/AjTIC9ox">Norepinephrine</a><a class="footnote-ref" id="fnref:26" href="#fn:26">26</a></li><li><a href="/facts/Phenethylamine/XyjysSul">Phenethylamine</a>†<a class="footnote-ref" id="fnref:27" href="#fn:27">27</a><a class="footnote-ref" id="fnref:28" href="#fn:28">28</a></li><li><a href="/facts/Trimethylamine/cj1dWmJq">Trimethylamine</a>†<a class="footnote-ref" id="fnref:29" href="#fn:29">29</a><a class="footnote-ref" id="fnref:30" href="#fn:30">30</a><a class="footnote-ref" id="fnref:31" href="#fn:31">31</a></li><li><a href="/facts/Tyramine/4qCvDzcl">Tyramine</a><a class="footnote-ref" id="fnref:32" href="#fn:32">32</a><a class="footnote-ref" id="fnref:33" href="#fn:33">33</a><a class="footnote-ref" id="fnref:34" href="#fn:34">34</a></li></ul>Notable exogenous <a href="/facts/Xenobiotic/0M2LAyEx">xenobiotics</a><ul><li><a href="/facts/Amphetamine/yKIpLJ9E">Amphetamine</a>† and its hydroxylamine <a href="/facts/Metabolic_intermediate/PjlX9C08">intermediate</a><a class="footnote-ref" id="fnref:35" href="#fn:35">35</a><a class="footnote-ref" id="fnref:36" href="#fn:36">36</a></li><li><a href="/facts/Benzydamine/MCULCCk2">Benzydamine</a><a class="footnote-ref" id="fnref:37" href="#fn:37">37</a><a class="footnote-ref" id="fnref:38" href="#fn:38">38</a></li><li><a href="/facts/Cimetidine/MX2vzIVg">Cimetidine</a><a class="footnote-ref" id="fnref:39" href="#fn:39">39</a><a class="footnote-ref" id="fnref:40" href="#fn:40">40</a></li><li><a href="/facts/Clozapine/N0Lqztg1">Clozapine</a><a class="footnote-ref" id="fnref:41" href="#fn:41">41</a><a class="footnote-ref" id="fnref:42" href="#fn:42">42</a></li><li>N-Deacetyl <a href="/facts/Ketoconazole/UQcvnER5">ketoconazole</a><a class="footnote-ref" id="fnref:43" href="#fn:43">43</a></li><li><a href="/facts/DMXAA/bN4rNysk">DMXAA</a>†<a class="footnote-ref" id="fnref:44" href="#fn:44">44</a><a class="footnote-ref" id="fnref:45" href="#fn:45">45</a></li><li><a href="/facts/Ethionamide/oD4HRy79">Ethionamide</a><a class="footnote-ref" id="fnref:46" href="#fn:46">46</a><a class="footnote-ref" id="fnref:47" href="#fn:47">47</a></li><li><a href="/facts/Itopride/2FEPSA8S">Itopride</a><a class="footnote-ref" id="fnref:48" href="#fn:48">48</a><a class="footnote-ref" id="fnref:49" href="#fn:49">49</a></li><li><a href="/facts/Methamphetamine/vS1jloMe">Methamphetamine</a> and its hydroxylamine intermediate<a class="footnote-ref" id="fnref:50" href="#fn:50">50</a><a class="footnote-ref" id="fnref:51" href="#fn:51">51</a></li><li><a href="/facts/Methimazole/xfFBnLl3">Methimazole</a><a class="footnote-ref" id="fnref:52" href="#fn:52">52</a><a class="footnote-ref" id="fnref:53" href="#fn:53">53</a></li><li><a href="/facts/Nicotine/VQ6HcIrY">Nicotine</a> – only the (S)-(−)-nicotine <a href="/facts/Enantiomer/wjPv5J3y">enantiomer</a><a class="footnote-ref" id="fnref:54" href="#fn:54">54</a><a class="footnote-ref" id="fnref:55" href="#fn:55">55</a></li><li><a href="/facts/Olopatadine/J4oxWdXt">Olopatadine</a><a class="footnote-ref" id="fnref:56" href="#fn:56">56</a></li><li><a href="/facts/Phenothiazines/SXgRQEeb">Phenothiazines</a> – 2-(Trifluoromethyl) <a href="/facts/Structural_analog/3aysWSVG">analogs</a><a class="footnote-ref" id="fnref:57" href="#fn:57">57</a></li><li><a href="/facts/Ranitidine/rddBabbF">Ranitidine</a><a class="footnote-ref" id="fnref:58" href="#fn:58">58</a><a class="footnote-ref" id="fnref:59" href="#fn:59">59</a></li><li><a href="/facts/Sulindac/b2ecGk1b">Sulindac</a> sulfide<a class="footnote-ref" id="fnref:60" href="#fn:60">60</a><a class="footnote-ref" id="fnref:61" href="#fn:61">61</a></li><li><a href="/facts/Tamoxifen/oHU8n7ch">Tamoxifen</a><a class="footnote-ref" id="fnref:62" href="#fn:62">62</a><a class="footnote-ref" id="fnref:63" href="#fn:63">63</a></li><li>Thiobenzamide<a class="footnote-ref" id="fnref:64" href="#fn:64">64</a></li><li><a href="/facts/Xanomeline/UuG9SYzB">Xanomeline</a><a class="footnote-ref" id="fnref:65" href="#fn:65">65</a></li></ul></td><td><ul><li><a href="/facts/Thiourea/69a3dfSc">Thiourea</a><a class="footnote-ref" id="fnref:66" href="#fn:66">66</a></li><li><a href="/facts/Indole-3-carbinol/mWClxmzK">Indole-3-carbinol</a><a class="footnote-ref" id="fnref:67" href="#fn:67">67</a></li><li></li></ul></td><td><ul><li></li><li></li></ul></td><td><ul><li><a href="/facts/Chlorpromazine/oFja1FYA">Chlorpromazine</a><a class="footnote-ref" id="fnref:68" href="#fn:68">68</a></li><li><a href="/facts/Imipramine/3ppWvEKp">Imipramine</a><a class="footnote-ref" id="fnref:69" href="#fn:69">69</a></li></ul></td></tr><tr><th scope="col" colspan="4">A † indicates moderate to complete selectivity for FMO3 relative to other <a href="/facts/Flavin-containing_monooxygenase/C2nIX3MI">FMO</a> isoenzymes.</th></tr></tbody></table>
<h2 id="cancer">Cancer</h2>
The FMO3 gene has been observed progressively downregulated in <a href="/facts/Human_papillomavirus/7XW8mjG2">human papillomavirus</a>-positive <a href="/facts/Neoplasm/K0ytzmPz">neoplastic</a> keratinocytes derived from uterine cervical <a href="/facts/Cervical_intraepithelial_neoplasia/6GoARC51">preneoplastic lesions</a> at different levels of malignancy.<a class="footnote-ref" id="fnref:70" href="#fn:70">70</a> For this reason, FMO3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for progression of uterine cervical preneoplastic lesions.<a class="footnote-ref" id="fnref:71" href="#fn:71">71</a>

<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/Flavin-containing_monooxygenase/C2nIX3MI">Flavin-containing monooxygenase</a></li>
<li><a href="/facts/Trimethylaminuria/FQs2Gkn1">Trimethylaminuria</a></li></ul>

<h2 id="further-reading">Further reading</h2>

<ul><li>Cashman JR, Park SB, Berkman CE, Cashman LE (1995). "Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism in adult humans". Chem. Biol. Interact. 96 (1): 33–46. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1995CBI....96...33C">1995CBI....96...33C</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0009-2797%2894%2903581-R">10.1016/0009-2797(94)03581-R</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7720103">7720103</a>.</li>
<li>Cashman JR (2004). "The implications of polymorphisms in mammalian flavin-containing monooxygenases in drug discovery and development". Drug Discov. Today. 9 (13): 574–81. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS1359-6446%2804%2903136-8">10.1016/S1359-6446(04)03136-8</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15203093">15203093</a>.</li>
<li>Zhou J, Shephard EA (2006). "Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3". Mutat. Res. 612 (3): 165–71. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2006MRRMR.612..165Z">2006MRRMR.612..165Z</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.mrrev.2005.09.001">10.1016/j.mrrev.2005.09.001</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16481213">16481213</a>.</li>
<li>Lomri N, Gu Q, Cashman JR (1992). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC48517">"Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver"</a>. Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1685–9. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1992PNAS...89.1685L">1992PNAS...89.1685L</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.89.5.1685">10.1073/pnas.89.5.1685</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC48517">48517</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1542660">1542660</a>.</li>
<li>Humbert JA, Hammond KB, Hathaway WE (1970). "Trimethylaminuria: the fish-odour syndrome". Lancet. 2 (7676): 770–1. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0140-6736%2870%2990241-2">10.1016/S0140-6736(70)90241-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/4195988">4195988</a>.</li>
<li>Higgins T, Chaykin S, Hammond KB, Humbert JR (1972). "Trimethylamine N-oxide synthesis: a human variant". Biochemical Medicine. 6 (4): 392–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-2944%2872%2990025-7">10.1016/0006-2944(72)90025-7</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/5048998">5048998</a>.</li>
<li>Lomri N, Gu Q, Cashman JR (1995). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40912">"Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver"</a>. Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9910. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.92.21.9910">10.1073/pnas.92.21.9910</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40912">40912</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7568243">7568243</a>.</li>
<li>Bhamre S, Bhagwat SV, Shankar SK, et al. (1995). "Flavin-containing monooxygenase mediated metabolism of psychoactive drugs by human brain microsomes". Brain Res. 672 (1–2): 276–80. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-8993%2894%2901135-5">10.1016/0006-8993(94)01135-5</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7749747">7749747</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:14938474">14938474</a>.</li>
<li>Cashman JR, Park SB, Yang ZC, et al. (1993). "Chemical, enzymatic, and human enantioselective S-oxygenation of cimetidine". Drug Metab. Dispos. 21 (4): 587–97. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0090-9556%2825%2907460-4">10.1016/S0090-9556(25)07460-4</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8104117">8104117</a>.</li>
<li>Park SB, Jacob P, Benowitz NL, Cashman JR (1994). "Stereoselective metabolism of (S)-(−)-nicotine in humans: formation of trans-(S)-(−)-nicotine N-1'-oxide". Chem. Res. Toxicol. 6 (6): 880–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1021%2Ftx00036a019">10.1021/tx00036a019</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8117928">8117928</a>.</li>
<li>Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0378-1119%2894%2990802-8">10.1016/0378-1119(94)90802-8</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8125298">8125298</a>.</li>
<li>Dolphin CT, Cullingford TE, Shephard EA, et al. (1996). "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. 235 (3): 683–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1432-1033.1996.00683.x">10.1111/j.1432-1033.1996.00683.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8654418">8654418</a>.</li>
<li>Chung WG, Cha YN (1997). "Oxidation of caffeine to theobromine and theophylline is catalyzed primarily by flavin-containing monooxygenase in liver microsomes". Biochem. Biophys. Res. Commun. 235 (3): 685–8. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1997BBRC..235..685C">1997BBRC..235..685C</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fbbrc.1997.6866">10.1006/bbrc.1997.6866</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9207220">9207220</a>.</li>
<li>Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0378-1119%2897%2900411-3">10.1016/S0378-1119(97)00411-3</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9373149">9373149</a>.</li>
<li>Treacy EP, Akerman BR, Chow LM, et al. (1998). <a href="https://doi.org/10.1093%2Fhmg%2F7.5.839">"Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication"</a>. Hum. Mol. Genet. 7 (5): 839–45. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Fhmg%2F7.5.839">10.1093/hmg/7.5.839</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9536088">9536088</a>.</li>
<li>Akerman BR, Forrest S, Chow L, et al. (1999). <a href="https://doi.org/10.1002%2F%28SICI%291098-1004%281999%2913%3A5%3C376%3A%3AAID-HUMU5%3E3.0.CO%3B2-A">"Two novel mutations of the FMO3 gene in a proband with trimethylaminuria"</a>. Hum. Mutat. 13 (5): 376–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2F%28SICI%291098-1004%281999%2913%3A5%3C376%3A%3AAID-HUMU5%3E3.0.CO%3B2-A">10.1002/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10338091">10338091</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:29584757">29584757</a>.</li></ul>

<h2 id="external-links">External links</h2>
<ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=Trimethylamine+monooxygenase">Trimethylamine+monooxygenase</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li>
<li><a href="https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=trimethylaminuria">Primary Trimethylaminuria (FMO3 Deficiency)</a> – NCBI bookshelf <a href="/facts/GeneReviews/vUoAKrF5">GeneReviews</a> entry</li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1">Shephard EA, Dolphin CT, Fox MF, Povey S, Smith R, Phillips IR (June 1993). "Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q". Genomics. 16 (1): 85–9. doi:10.1006/geno.1993.1144. PMID 8486388. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></li>
<li id="fn:2">Dolphin CT, Riley JH, Smith RL, Shephard EA, Phillips IR (February 1998). "Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA". Genomics. 46 (2): 260–7. doi:10.1006/geno.1997.5031. PMID 9417913. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></li>
<li id="fn:3">"Entrez Gene: FMO3 flavin containing monooxygenase 3". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2328" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2328</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></li>
<li id="fn:4">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></li>
<li id="fn:5">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></li>
<li id="fn:6">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></li>
<li id="fn:7">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></li>
<li id="fn:8">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></li>
<li id="fn:9">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></li>
<li id="fn:10">Cashman JR (September 2000). "Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181–191. doi:10.2174/1389200003339135. PMID 11465082. Human FMO3 N-oxygenates primary, secondary and tertiary amines whereas human FMO1 is only highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S-oxygenate a number of nucleophilic sulfur-containing substrates and in some cases, does so with great stereoselectivity. ... For amines with smaller aromatic substituents such as phenethylamines, often these compounds are efficiently N-oxygenated by human FMO3. ... (S)-Nicotine N-1'-oxide formation can also be used as a highly stereoselective probe of human FMO3 function for adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or ranitidine N-oxidation can also be used as a functional probe of human FMO3. With the recent observation of human FMO3 genetic polymorphism and poor metabolism phenotype in certain human populations, variant human FMO3 may contribute to adverse drug reactions or exaggerated clinical response to certain medications. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></li>
<li id="fn:11">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></li>
<li id="fn:12">Cashman JR (September 2000). "Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181–191. doi:10.2174/1389200003339135. PMID 11465082. Human FMO3 N-oxygenates primary, secondary and tertiary amines whereas human FMO1 is only highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S-oxygenate a number of nucleophilic sulfur-containing substrates and in some cases, does so with great stereoselectivity. ... For amines with smaller aromatic substituents such as phenethylamines, often these compounds are efficiently N-oxygenated by human FMO3. ... (S)-Nicotine N-1'-oxide formation can also be used as a highly stereoselective probe of human FMO3 function for adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or ranitidine N-oxidation can also be used as a functional probe of human FMO3. With the recent observation of human FMO3 genetic polymorphism and poor metabolism phenotype in certain human populations, variant human FMO3 may contribute to adverse drug reactions or exaggerated clinical response to certain medications. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></li>
<li id="fn:13">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></li>
<li id="fn:14">Zhou S, Kestell P, Paxton JW (July 2002). "6-methylhydroxylation of the anti-cancer agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by flavin-containing monooxygenase 3". Eur J Drug Metab Pharmacokinet. 27 (3): 179–183. doi:10.1007/bf03190455. PMID 12365199. S2CID 21583717. Only FMO3 formed 6-OH-MXAA at a similar rate to that in cDNA-expressed cytochromes P-450 (CYP)1A2. The results of this study indicate that human FMO3 has the capacity to form 6-OH-MXAA, but plays a lesser important role for this reaction than CYP1A2 that has been demonstrated to catalyse 6-OH-MXAA formation. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></li>
<li id="fn:15">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></li>
<li id="fn:16">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></li>
<li id="fn:17">Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen SL, Lusis AJ (2013). "Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation". Cell Metab. 17 (1): 49–60. doi:10.1016/j.cmet.2012.12.011. PMC 3771112. PMID 23312283. Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis. We now examine genetic, dietary, and hormonal factors regulating TMAO levels. We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO. Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771112" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771112</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></li>
<li id="fn:18">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></li>
<li id="fn:19">Dolphin CT, Janmohamed A, Smith RL, Shephard EA, Phillips IR (1997). "Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome". Nat. Genet. 17 (4): 491–4. doi:10.1038/ng1297-491. PMID 9398858. S2CID 24732203. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></li>
<li id="fn:20">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></li>
<li id="fn:21">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></li>
<li id="fn:22">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></li>
<li id="fn:23">Glennon RA (2013). "Phenylisopropylamine stimulants: amphetamine-related agents". In Lemke TL, Williams DA, Roche VF, Zito W (eds.). Foye's principles of medicinal chemistry (7th ed.). Philadelphia, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 646–648. ISBN 978-1-60913-345-0. The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. <a href="978-1-60913-345-0" target="_blank">978-1-60913-345-0</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></li>
<li id="fn:24">Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication". J. Pharmacol. Exp. Ther. 288 (3): 1251–1260. doi:10.1016/S0022-3565(24)38081-4. PMID 10027866. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></li>
<li id="fn:25">Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></li>
<li id="fn:26">Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></li>
<li id="fn:27">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></li>
<li id="fn:28">Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></li>
<li id="fn:29">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></li>
<li id="fn:30">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></li>
<li id="fn:31">Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></li>
<li id="fn:32">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></li>
<li id="fn:33">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></li>
<li id="fn:34">Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, Yeung CK (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981377</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></li>
<li id="fn:35">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:35" class="footnote-back-ref">↩</a></li>
<li id="fn:36">Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication". J. Pharmacol. Exp. Ther. 288 (3): 1251–1260. doi:10.1016/S0022-3565(24)38081-4. PMID 10027866. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></li>
<li id="fn:37">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></li>
<li id="fn:38">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:38" class="footnote-back-ref">↩</a></li>
<li id="fn:39">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:39" class="footnote-back-ref">↩</a></li>
<li id="fn:40">Cashman JR (September 2000). "Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181–191. doi:10.2174/1389200003339135. PMID 11465082. Human FMO3 N-oxygenates primary, secondary and tertiary amines whereas human FMO1 is only highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S-oxygenate a number of nucleophilic sulfur-containing substrates and in some cases, does so with great stereoselectivity. ... For amines with smaller aromatic substituents such as phenethylamines, often these compounds are efficiently N-oxygenated by human FMO3. ... (S)-Nicotine N-1'-oxide formation can also be used as a highly stereoselective probe of human FMO3 function for adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or ranitidine N-oxidation can also be used as a functional probe of human FMO3. With the recent observation of human FMO3 genetic polymorphism and poor metabolism phenotype in certain human populations, variant human FMO3 may contribute to adverse drug reactions or exaggerated clinical response to certain medications. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:40" class="footnote-back-ref">↩</a></li>
<li id="fn:41">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:41" class="footnote-back-ref">↩</a></li>
<li id="fn:42">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:42" class="footnote-back-ref">↩</a></li>
<li id="fn:43">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:43" class="footnote-back-ref">↩</a></li>
<li id="fn:44">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:44" class="footnote-back-ref">↩</a></li>
<li id="fn:45">Zhou S, Kestell P, Paxton JW (July 2002). "6-methylhydroxylation of the anti-cancer agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by flavin-containing monooxygenase 3". Eur J Drug Metab Pharmacokinet. 27 (3): 179–183. doi:10.1007/bf03190455. PMID 12365199. S2CID 21583717. Only FMO3 formed 6-OH-MXAA at a similar rate to that in cDNA-expressed cytochromes P-450 (CYP)1A2. The results of this study indicate that human FMO3 has the capacity to form 6-OH-MXAA, but plays a lesser important role for this reaction than CYP1A2 that has been demonstrated to catalyse 6-OH-MXAA formation. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:45" class="footnote-back-ref">↩</a></li>
<li id="fn:46">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:46" class="footnote-back-ref">↩</a></li>
<li id="fn:47">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:47" class="footnote-back-ref">↩</a></li>
<li id="fn:48">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:48" class="footnote-back-ref">↩</a></li>
<li id="fn:49">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:49" class="footnote-back-ref">↩</a></li>
<li id="fn:50">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:50" class="footnote-back-ref">↩</a></li>
<li id="fn:51">Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication". J. Pharmacol. Exp. Ther. 288 (3): 1251–1260. doi:10.1016/S0022-3565(24)38081-4. PMID 10027866. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:51" class="footnote-back-ref">↩</a></li>
<li id="fn:52">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:52" class="footnote-back-ref">↩</a></li>
<li id="fn:53">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:53" class="footnote-back-ref">↩</a></li>
<li id="fn:54">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:54" class="footnote-back-ref">↩</a></li>
<li id="fn:55">Cashman JR (September 2000). "Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181–191. doi:10.2174/1389200003339135. PMID 11465082. Human FMO3 N-oxygenates primary, secondary and tertiary amines whereas human FMO1 is only highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S-oxygenate a number of nucleophilic sulfur-containing substrates and in some cases, does so with great stereoselectivity. ... For amines with smaller aromatic substituents such as phenethylamines, often these compounds are efficiently N-oxygenated by human FMO3. ... (S)-Nicotine N-1'-oxide formation can also be used as a highly stereoselective probe of human FMO3 function for adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or ranitidine N-oxidation can also be used as a functional probe of human FMO3. With the recent observation of human FMO3 genetic polymorphism and poor metabolism phenotype in certain human populations, variant human FMO3 may contribute to adverse drug reactions or exaggerated clinical response to certain medications. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:55" class="footnote-back-ref">↩</a></li>
<li id="fn:56">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:56" class="footnote-back-ref">↩</a></li>
<li id="fn:57">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:57" class="footnote-back-ref">↩</a></li>
<li id="fn:58">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:58" class="footnote-back-ref">↩</a></li>
<li id="fn:59">Cashman JR (September 2000). "Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism". Curr. Drug Metab. 1 (2): 181–191. doi:10.2174/1389200003339135. PMID 11465082. Human FMO3 N-oxygenates primary, secondary and tertiary amines whereas human FMO1 is only highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S-oxygenate a number of nucleophilic sulfur-containing substrates and in some cases, does so with great stereoselectivity. ... For amines with smaller aromatic substituents such as phenethylamines, often these compounds are efficiently N-oxygenated by human FMO3. ... (S)-Nicotine N-1'-oxide formation can also be used as a highly stereoselective probe of human FMO3 function for adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or ranitidine N-oxidation can also be used as a functional probe of human FMO3. With the recent observation of human FMO3 genetic polymorphism and poor metabolism phenotype in certain human populations, variant human FMO3 may contribute to adverse drug reactions or exaggerated clinical response to certain medications. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:59" class="footnote-back-ref">↩</a></li>
<li id="fn:60">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:60" class="footnote-back-ref">↩</a></li>
<li id="fn:61">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:61" class="footnote-back-ref">↩</a></li>
<li id="fn:62">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:62" class="footnote-back-ref">↩</a></li>
<li id="fn:63">Hisamuddin IM, Yang VW (June 2007). "Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives". Pharmacogenomics. 8 (6): 635–643. doi:10.2217/14622416.8.6.635. PMC 2213907. PMID 17559352. Other drug substrates have been used for both in vitro and in vivo analyses. ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its polymorphisms have been widely studied [8,12,13]. This enzyme has a wide substrate specificity, including the dietary-derived tertiary amines trimethylamine, tyramine and nicotine; commonly used drugs including cimetidine, ranitidine, clozapine, methimazole, itopride, ketoconazole, tamoxifen and sulindac sulfide; and agrichemicals, such as organophosphates and carbamates [14–22]. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213907</a> <a href="#fnref:63" class="footnote-back-ref">↩</a></li>
<li id="fn:64">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:64" class="footnote-back-ref">↩</a></li>
<li id="fn:65">Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. A second precaution with respect to predicting FMO enzyme substrate specificity is that factors other than size and charge must play a role, but these parameters are not well understood. An example is the high selectivity observed with human FMO3, compared to the other FMO enzymes, in the N-oxygenation of the important constitutive substrate trimethylamine (Lang et al., 1998). ... The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b). ... Of particular significance for this review is that individuals homozygous for certain FMO3 allelic variants (e.g., null variants) also demonstrate impaired metabolism toward other FMO substrates including ranitidine, nicotine, thio-benzamide, and phenothiazine derivatives (Table 4; Cashman et al., 1995, 2000; Kang et al., 2000; Cashman, 2002; Park et al., 2002; Lattard et al., 2003a, 2003b). ... The metabolic activation of ethionamide by the bacterial FMO is the same as the mammalian FMO activation of thiobenzamide to produce hepatotoxic sulfinic and sulfinic acid metabolites. Not surprisingly, Dr. Ortiz de Montellano's laboratory and our own have found ethionamide to be a substrate for human FMO1, FMO2, and FMO3 (unpublished observations).Table 5: N-containing drugs and xenobiotics oxygenated by FMOTable 6: S-containing drugs and xenobiotics oxygenated by FMOTable 7: FMO activities not involving S- or N-oxygenation <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602</a> <a href="#fnref:65" class="footnote-back-ref">↩</a></li>
<li id="fn:66">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:66" class="footnote-back-ref">↩</a></li>
<li id="fn:67">Cashman JR, Xiong Y, Lin J, Verhagen H, Van Poppel G, Van Bladeren PJ, Larsen-Su S, Williams DE (September 1999). In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles. Vol. 58. pp. 1047–1055. doi:10.1016/s0006-2952(99)00166-5. PMID 10509757. Retrieved 15 April 2024. After a 3-week run-in period, 5 volunteers continued on a glucosinolate-free diet for 3 weeks (control group), and 5 others consumed 300 g of cooked Brussels sprouts per day (sprouts group). Human flavin-containing monooxygenase activity was measured by determining the levels of urinary trimethylamine and trimethylamine N-oxide. In the control group similar trimethylamine to trimethylamine N-oxide ratios were observed, while in the sprouts group the trimethylamine to trimethylamine N-oxide ratios were increased 2.6- to 3.2-fold, and thus flavin-containing monooxygenase functional activity was decreased significantly. {{cite encyclopedia}}: |journal= ignored (help) <a href="https://pubmed.ncbi.nlm.nih.gov/10509757/" target="_blank">https://pubmed.ncbi.nlm.nih.gov/10509757/</a> <a href="#fnref:67" class="footnote-back-ref">↩</a></li>
<li id="fn:68">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:68" class="footnote-back-ref">↩</a></li>
<li id="fn:69">Trimethylamine monooxygenase (Homo sapiens) | BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 18 September 2016. trimethylaminuria (fish-odor syndrome) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase ... FMO3 deficiency results in trimethylaminuria or the fish-like odour syndrome ... isozyme FMO3 regulates the conversion of N,N,N-trimethylamine into its N-oxide and hence controls the release of volatile N,N,N-trimethylamine from the individual <a href="http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0" target="_blank">http://www.brenda-enzymes.info/enzyme.php?ecno=1.14.13.148&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0</a> <a href="#fnref:69" class="footnote-back-ref">↩</a></li>
<li id="fn:70">Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808. hdl:11392/2066612. PMID 25205602. S2CID 24986454. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:70" class="footnote-back-ref">↩</a></li>
<li id="fn:71">Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808. hdl:11392/2066612. PMID 25205602. S2CID 24986454. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:71" class="footnote-back-ref">↩</a></li>
</ol>

Flavin-containing monooxygenase 3 open-in-new

Flavin-containing monooxygenase 3