Trimethylaminuria and a human FMO3 mutation database
Trimethylaminuria and a human FMO3 mutation database
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DOI：
10.1002/humu.10252
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发表时间：
2003-01-01
期刊：
影响因子：
3.9
通讯作者：
Phillips, IR
中科院分区：
文献类型：
--
作者：
Hernandez, D;Addou, S;Phillips, IR
三甲氨基尿症(TMAuria)，或鱼腥症，是由于含有黄素的单加氧酶3(FMO3)缺陷引起的。在肝脏中，这种蛋白质催化肠道中来自饮食来源的气味三甲胺(TMA)的NADPH依赖的氧化代谢，生成无味的三甲胺N氧化物(TMA N氧化物)。受影响的人无法进行这种反应，因此散发出鱼腥味，因为他们的呼吸和汗液中分泌TMA，并在他们的尿液中排泄。这导致了各种心理社会问题，包括学校教育中断、临床抑郁和自杀未遂。已知有12个错义突变、3个无义突变和1个大的缺失突变导致TMAURIA。FMO3也是一种药物代谢酶，活性受损预计会对TMAuric患者和普通人群的药物治疗效果和药物不良反应的可能性产生影响。到目前为止，已有8个与TMAuria无关的多态变异被报道。人类FMO3突变数据库是使用MuStar创建的，MuStar是一个特定于座位的数据库系统，用于维护等位基因变异的数据并通过万维网分发这些数据。该数据库目前包含24个条目，可通过网址http://human-fmo3.biochem.ucl.ac.Uk/Human-FMO3.在万维网上访问其他条目可通过数据库管理员或通过基于网络的表格提交。(C)2003年Wiley-Liss，Inc.
Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.Uk/Human-FMO3. Additional entries can be submitted via the curator of the database or via a web-based form. (C) 2003 Wiley-Liss, Inc.