Trimethylamine N-oxide
(Synonyms: 三甲胺N-氧化物) 目录号 : GC40928
A metabolite of choline, phosphatidylcholine, and L-carnitine
Cas No.:1184-78-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Trimethylamine N-oxide (TMAO) is a product of the oxidation of TMA by flavin-containing mono-oxygenase 3 in the liver. TMAO levels predict risk for atherosclerosis and are elevated in patients with chronic kidney disease and obesity. TMAO levels are decreased in ulcerative colitis. TMAO increases atherosclerosis in ApoE-/- mice, suggesting that TMAO can directly induce cardiovascular disease. The biosynthesis of TMA is dependent on gut bacteria, providing a link between the biome and cardiovascular disease.
三甲胺氧化物（TMAO）是肝脏中经过黄酮单加氧酶3氧化三甲胺生成的产物。TMAO水平可预测动脉粥样硬化风险，并在慢性肾脏病和肥胖症患者中升高。而在溃疡性结肠炎中TMAO水平则降低。TMAO能够增加ApoE-/-小鼠的动脉粥样硬化程度，表明TMAO能够直接诱导心血管疾病。TMA的生物合成依赖于肠道细菌，从而提供了肠道菌群与心血管疾病之间的联系。
| Cas No. | 1184-78-7 | SDF | |
| 别名 | 三甲胺N-氧化物 | ||
| Canonical SMILES | C[N](C)(C)=O | ||
| 分子式 | C3H9NO | 分子量 | 75.1 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,Ethanol: 25 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 13.3156 mL | 66.5779 mL | 133.1558 mL |
| 5 mM | 2.6631 mL | 13.3156 mL | 26.6312 mL |
| 10 mM | 1.3316 mL | 6.6578 mL | 13.3156 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The microbial metabolite Trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer
Cell Metab 2022 Apr 5;34(4):581-594.e8.PMID:35278352DOI:10.1016/j.cmet.2022.02.010.
Immunotherapy has achieved limited success in patients with triple-negative breast cancer (TNBC), an aggressive disease with a poor prognosis. Commensal microbiota have been proven to colonize the mammary gland, but whether and how they modulate the tumor microenvironment remains elusive. We performed a multiomics analysis of a cohort of patients with TNBC (n = 360) and found genera under Clostridiales, and the related metabolite Trimethylamine N-oxide (TMAO) was more abundant in tumors with an activated immune microenvironment. Patients with higher plasma TMAO achieved better responses to immunotherapy. Mechanistically, TMAO induced pyroptosis in tumor cells by activating the endoplasmic reticulum stress kinase PERK and thus enhanced CD8+ T cell-mediated antitumor immunity in TNBC in vivo. Collectively, our findings offer new insights into microbiota-metabolite-immune crosstalk and indicate that microbial metabolites, such as TMAO or its precursor choline, may represent a novel therapeutic strategy to promote the efficacy of immunotherapy in TNBC.
Trimethylamine N-oxide (TMAO), Diet and Cardiovascular Disease
Curr Atheroscler Rep 2021 Feb 17;23(4):12.PMID:33594574DOI:10.1007/s11883-021-00910-x.
Purpose of review: The association between plasma Trimethylamine N-oxide (TMAO), diet and risk for cardiovascular disease (CVD) is still not fully understood. While epidemiologic research shows a causal relationship between plasma TMAO concentrations and CVD risk, the role of dietary precursors in determining plasma concentrations of TMAO and biomarkers for CVD is inconclusive. Recent findings: Studies in diverse populations show that plasma TMAO concentrations are positively associated with inflammation, endothelial dysfunction, type-2 diabetes, central adiposity and hypertension. Most recent studies utilizing challenges of dietary choline have not shown increases in plasma chronic TMAO concentrations while studies with carnitine have shown increases in plasma TMAO but in some cases, no alterations in plasma lipids or biomarkers of oxidative stress were observed. TMAO is an important plasma metabolite that through several mechanisms can increase the risk of CVD. The correlations between dietary choline and carnitine on chronic plasma TMAO levels and risk for CVD requires further investigation.
Trimethylamine N-oxide Binds and Activates PERK to Promote Metabolic Dysfunction
Cell Metab 2019 Dec 3;30(6):1141-1151.e5.PMID:31543404DOI:10.1016/j.cmet.2019.08.021.
The gut-microbe-derived metabolite Trimethylamine N-oxide (TMAO) is increased by insulin resistance and associated with several sequelae of metabolic syndrome in humans, including cardiovascular, renal, and neurodegenerative disease. The mechanism by which TMAO promotes disease is unclear. We now reveal the endoplasmic reticulum stress kinase PERK (EIF2AK3) as a receptor for TMAO: TMAO binds to PERK at physiologically relevant concentrations; selectively activates the PERK branch of the unfolded protein response; and induces the transcription factor FoxO1, a key driver of metabolic disease, in a PERK-dependent manner. Furthermore, interventions to reduce TMAO, either by manipulation of the gut microbiota or by inhibition of the TMAO synthesizing enzyme, flavin-containing monooxygenase 3, can reduce PERK activation and FoxO1 levels in the liver. Taken together, these data suggest TMAO and PERK may be central to the pathogenesis of the metabolic syndrome.
Trimethylamine N-oxide in cardiovascular disease
Adv Clin Exp Med 2022 Aug;31(8):913-925.PMID:35438848DOI:10.17219/acem/147666.
Although traditional cardiovascular risk factors are well established and understood, mortality and morbidity in patients with cardiovascular disease (CVD) remains high. Exploring new pathophysiological pathways enables a better understanding of CVD at both the molecular and clinical levels. Gut microbiota as a potential modulator of CVD are the subject of extensive research. In recent years, Trimethylamine N-oxide (TMAO), a biologically active molecule generated by the gut microbiota, has been widely tested in studies on various populations of patients. The ultimate TMAO levels depend on individual features and gut microbiota composition. Most of the research on TMAO has focused on atherosclerotic CVD and heart failure (HF). Studies conducted so far support the use of TMAO as a prognostic marker in CVD. Several studies describe diverse interventions aimed at reducing the concentration of TMAO and its harmful effects. This article summarizes the findings from research, discusses the major insights into TMAO metabolism and related pathophysiological processes, as well as indicates the directions for future research.
Gut Microbial Metabolite Trimethylamine N-oxide Aggravates Pulmonary Hypertension
Am J Respir Cell Mol Biol 2022 Apr;66(4):452-460.PMID:35100519DOI:10.1165/rcmb.2021-0414OC.
Trimethylamine N-oxide (TMAO), a metabolite derived from intestine microbial flora, enhances vascular inflammation in a variety of cardiovascular diseases, and the bacterial communities associated with TMAO metabolism are higher in pulmonary hypertension (PH) patients. The effects of TMAO on PH, however, have not been elucidated. In the present study, circulating TMAO was found to be elevated in intermediate to high-risk PH patients when compared with healthy control or low-risk PH patients. In monocrotaline-induced rat PH models, circulating TMAO was elevated; and reduction of TMAO using 3,3-dimethyl-1-butanol (DMB) significantly decreased right ventricle systolic pressure and pulmonary vascular muscularization in both monocrotaline-induced rat PH and hypoxia-induced mouse PH models. RNA sequencing of rat lungs revealed that DMB treatment significantly suppressed the pathways involved in cytokine-cytokine receptor interaction and in cytokine and chemokine signaling. Protein-protein interaction analysis of the differentially expressed transcripts regulated by DMB showed five hub genes with a strong connectivity of proinflammatory cytokines and chemokines, including Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6. In vitro, TMAO significantly increased the expression of Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6 in bone-marrow-derived macrophage. Also, TMAO-treated conditioned medium from macrophage increased the proliferation and migration of pulmonary artery smooth muscle cells, but TMAO treatment did not change the proliferation or migration of pulmonary artery smooth muscle cells. In conclusion, our study demonstrates that TMAO is increased in severe PH, and the reduction of TMAO decreases pulmonary vascular muscularization and alleviates PH by suppressing the macrophage production of chemokines and cytokines.