Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Uremic toxins such as 2-Hexenal are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性(未被国际癌症研究机构IARC列名)。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
长期暴露于尿毒症毒素可能会导致多种疾病,包括肾脏损伤、慢性肾病和心血管疾病。
Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
Diastereo- and Atroposelective Synthesis of Bridged Biaryls Bearing an Eight-Membered Lactone through an Organocatalytic Cascade
摘要:
We present herein an unprecedented stereoselective synthesis of bridged biaryls with defined axial and central chirality from readily available starting materials. This N-heterocyclic carbene-catalyzed method proceeds through propargylic substitution of azolium enolates followed by two-directional cyclization, as supported by DFT calculation. A range of benzofuran/indole-derived bridged biaryls bearing an eight-membered lactone are accessed with uniformly high stereoselectivity (>98:2 dr, mostly >98% ee).
Synthesis of 8-substituted xanthines via 5,6-diaminouracils: an efficient route to A2A adenosine receptor antagonists
作者:Ma Dong、Mikhail Sitkovsky、Amy E. Kallmerten、Graham B. Jones
DOI:10.1016/j.tetlet.2008.05.071
日期:2008.7
A one-pot route to 8-substituted xanthines has been developed from 5,6-diaminouracils and carboxaldehydes. The process, promoted by (bromodimethyl)sulfonium bromide, is mild and efficient and eliminates the need for external oxidants. Yields are good and the process is applicable to a range of substrates including a family of A2A adenosine receptor antagonists. Preparation of a new analog of the antagonist
作者:Bin Tan、Zugui Shi、Pei Juan Chua、Yongxin Li、Guofu Zhong
DOI:10.1002/anie.200805205
日期:2009.1.12
available α‐carbonyl oximes and α,β‐unsaturated aldehydes. The domino reaction proceeds through iminium activation of α,β‐unsaturated aldehydes, Michael addition using oximes as N‐selective nucleophiles, and aldolcondensation.
Application of a Flexible Synthesis of (5<i>R</i>)-Thiolactomycin To Develop New Inhibitors of Type I Fatty Acid Synthase
作者:Jill M. McFadden、Susan M. Medghalchi、Jagan N. Thupari、Michael L. Pinn、Aravinda Vadlamudi、Katherine I. Miller、Francis P. Kuhajda、Craig A. Townsend
DOI:10.1021/jm049389h
日期:2005.2.1
Fattyacid synthase (FAS) catalyzes the synthesis of palmitate from the sequential condensation of an acetyl primer with two carbon units added from malonyl-CoA. Inhibition of the beta-ketoacyl synthase domain of mammalian FAS leads to selective cytotoxicity to various cancer cell lines in vitro and in vivo. Also, inhibitors of FAS can cause reduced food intake and body weight in mice. Naturally occurring
Stereoselective Hydrosilylation of Enals and Enones Catalysed by Palladium Nanoparticles
作者:Meryem Benohoud、Sakari Tuokko、Petri M. Pihko
DOI:10.1002/chem.201100655
日期:2011.7.18
A highly versatile and efficient hydrosilylation method by palladium nanoparticle catalysis allows the direct and chemoselective synthesis of 1) enolsilanes of high isomeric purity, 2) saturated aldehydes or ketones, or 3) the corresponding saturated acetals from α,β‐unsaturated aldehydes or ketones. The choice of the product is determined by simply switching the solvent from THF to mixtures of THF/water
Engineering a nicotinamide mononucleotide redox cofactor system for biocatalysis
作者:William B. Black、Linyue Zhang、Wai Shun Mak、Sarah Maxel、Youtian Cui、Edward King、Bonnie Fong、Alicia Sanchez Martinez、Justin B. Siegel、Han Li
DOI:10.1038/s41589-019-0402-7
日期:2020.1
Biological production of chemicals often requires the use of cellular cofactors, such as nicotinamide adenine dinucleotide phosphate (NADP+). These cofactors are expensive to use in vitro and difficult to control in vivo. We demonstrate the development of a noncanonical redox cofactor system based on nicotinamidemononucleotide (NMN+). The key enzyme in the system is a computationally designed glucose dehydrogenase