1,3,7-Trimethyl-5-hydroxyisourate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1,3,7-Trimethyl-5-hydroxyisourate
• 英文别名: 5-hydroxy-1,3,7-trimethylpurine-2,6,8-trione
• 化学式: C₈H₁₀N₄O₄
• 分子量: 226.192
• InChiKey: XNXQVRHXDIDGDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,3,7-三甲基尿酸 在 乙醇 、 氧气 、 rose bengal 作用下， 生成 3-methyl-5--1,5-dehydrohydantoin 、 1,3-Dimethyl-1-(1-methyl-2,5-dioxoimidazol-4-yl)urea 、 1,3,7-Trimethyl-5-hydroxyisourate
  参考文献：
  名称：

  Rose Bengal 光敏氧化氧嘌呤

  摘要：

  研究了玫瑰红对氧代嘌呤 (OP) 作为咖啡因、茶碱、可可碱和 1,3,7-三甲基尿酸 (TMU) 的光敏氧化。在所有情况下，光氧化都是通过 II 型机制发生的。OP 在不同溶剂中测定了反应性和非反应性 1O2 淬灭速率常数。基于速率常数与不同溶剂参数（α, β, ET[30], AN, DN, *,）的相关性，提出了 1O2 和 OP 之间的激基复合物的初始形成，其演化为两性离子过渡态。对一些反应产物进行了表征，其中得到了 3-甲基-甲基-5-(甲胺)-1,5-脱氢乙内酰脲作为 TMU 的主要光氧化产物。提出了形成该反应产物和其他反应产物的反应机制。

  DOI：

  10.1111/j.1751-1097.1998.tb02501.x

文献信息

• Delineation of the Caffeine C-8 Oxidation Pathway in Pseudomonas sp. Strain CBB1 via Characterization of a New Trimethyluric Acid Monooxygenase and Genes Involved in Trimethyluric Acid Metabolism
  作者：Sujit Kumar Mohanty、Chi-Li Yu、Shuvendu Das、Tai Man Louie、Lokesh Gakhar、Mani Subramanian

  DOI：10.1128/jb.00597-12

  日期：2012.8

  The molecular basis of the ability of bacteria to live on caffeine via the C-8 oxidation pathway is unknown. The first step of this pathway, caffeine to trimethyluric acid (TMU), has been attributed to poorly characterized caffeine oxidases and a novel quinone-dependent caffeine dehydrogenase. Here, we report the detailed characterization of the second enzyme, a novel NADH-dependent trimethyluric acid monooxygenase (TmuM), a flavoprotein that catalyzes the conversion of TMU to 1,3,7-trimethyl-5-hydroxyisourate (TM-HIU). This product spontaneously decomposes to racemic 3,6,8-trimethylallantoin (TMA). TmuM prefers trimethyluric acids and, to a lesser extent, dimethyluric acids as substrates, but it exhibits no activity on uric acid. Homology models of TmuM against uric acid oxidase HpxO (which catalyzes uric acid to 5-hydroxyisourate) reveal a much bigger and hydrophobic cavity to accommodate the larger substrates. Genes involved in the caffeine C-8 oxidation pathway are located in a 25.2-kb genomic DNA fragment of CBB1, including cdhABC (coding for caffeine dehydrogenase) and tmuM (coding for TmuM). Comparison of this gene cluster to the uric acid-metabolizing gene cluster and pathway of Klebsiella pneumoniae revealed two major open reading frames coding for the conversion of TM-HIU to S -(+)-trimethylallantoin [ S -(+)-TMA]. The first one, designated tmuH , codes for a putative TM-HIU hydrolase, which catalyzes the conversion of TM-HIU to 3,6,8-trimethyl-2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (TM-OHCU). The second one, designated tmuD , codes for a putative TM-OHCU decarboxylase which catalyzes the conversion of TM-OHCU to S -(+)-TMA. Based on a combination of enzymology and gene-analysis, a new degradative pathway for caffeine has been proposed via TMU, TM-HIU, TM-OHCU to S -(+)-TMA.

  摘要 细菌能够通过 C-8 氧化途径以咖啡因为生的分子基础尚不清楚。该途径的第一步，即咖啡因转化为三甲基尿酸（TMU），一直归因于特征不清的咖啡因氧化酶和一种新型醌依赖性咖啡因脱氢酶。在这里，我们报告了第二种酶的详细特征，即新型 NADH 依赖性三甲基尿酸单加氧酶（TmuM），它是一种黄素蛋白，可催化 TMU 转化为 1,3,7-三甲基-5-羟基异尿酸（TM-HIU）。这种产物会自发分解成外消旋的 3,6,8-三甲基尿囊素（TMA）。TmuM 喜欢以三甲基尿酸为底物，其次是二甲基尿酸，但对尿酸没有活性。TmuM 与尿酸氧化酶 HpxO（催化尿酸转化为 5-羟基异酸酯）的同源模型显示，TmuM 有一个更大的疏水空腔，以容纳更大的底物。参与咖啡因 C-8 氧化途径的基因位于 CBB1 25.2-kb 的基因组 DNA 片段中，包括 cdhABC (咖啡因脱氢酶）和 tmuM (TmuM）。将该基因簇与肺炎克雷伯氏菌的尿酸代谢基因簇和途径进行比较 肺炎克雷伯菌 发现了两个主要的开放阅读框，它们编码将 TM-HIU 转化为 S -(+)-三甲基尿囊素 [ S -(+)-TMA]。第一个被命名为 tmuH 它催化 TM-HIU 转化为 3,6,8-三甲基-2-氧代-4-羟基-4-羧基-5-脲基咪唑啉（TM-OHCU）。第二种是 tmuD 编码的是一种假定的 TM-OHCU 脱羧酶，它能催化 TM-OHCU 转化为 S -(+)-TMA。根据酶学和基因分析相结合的方法，提出了咖啡因通过 TMU、TM-HIU、TM-OHCU 到 S -（+）-TMA 的新降解途径。 S -(+)-TMA。
• Genetic characterization of caffeine degradation by bacteria and its potential applications
  作者：Ryan M. Summers、Sujit K. Mohanty、Sridhar Gopishetty、Mani Subramanian

  DOI：10.1111/1751-7915.12262

  日期：2015.5

  SummaryThe ability of bacteria to grow on caffeine as sole carbon and nitrogen source has been known for over 40 years. Extensive research into this subject has revealed two distinct pathways, N‐demethylation and C‐8 oxidation, for bacterial caffeine degradation. However, the enzymological and genetic basis for bacterial caffeine degradation has only recently been discovered. This review article discusses the recent discoveries of the genes responsible for both N‐demethylation and C‐8 oxidation. All of the genes for the N‐demethylation pathway, encoding enzymes in the Rieske oxygenase family, reside on 13.2‐kb genomic DNA fragment found in Pseudomonas putida CBB5. A nearly identical DNA fragment, with homologous genes in similar orientation, is found in Pseudomonas sp. CES. Similarly, genes for C‐8 oxidation of caffeine have been located on a 25.2‐kb genomic DNA fragment of Pseudomonas sp. CBB1. The C‐8 oxidation genes encode enzymes similar to those found in the uric acid metabolic pathway of Klebsiella pneumoniae. Various biotechnological applications of these genes responsible for bacterial caffeine degradation, including bio‐decaffeination, remediation of caffeine‐contaminated environments, production of chemical and fuels and development of diagnostic tests have also been demonstrated.
• Photosensitized Oxidation of Oxopurines by Rose Bengal
  作者：Daniel H. Murgida、Pedro F. Aramendía、Rosa Erra Balsells

  DOI：10.1111/j.1751-1097.1998.tb02501.x

  日期：1998.10

  all cases photooxidations occur by a type II mechanism. Reactive and nonreactive 1O2 quenching rate constants by OP were determined in different solvents. Based on the correlations of the rate constants with different solvent parameters (α, β, ET[30], AN, DN, *,), the initial formation of an exciplex between 1O2 and OP is proposed that evolves to a zwitterionic transition state. Some reaction products

  研究了玫瑰红对氧代嘌呤 (OP) 作为咖啡因、茶碱、可可碱和 1,3,7-三甲基尿酸 (TMU) 的光敏氧化。在所有情况下，光氧化都是通过 II 型机制发生的。OP 在不同溶剂中测定了反应性和非反应性 1O2 淬灭速率常数。基于速率常数与不同溶剂参数（α, β, ET[30], AN, DN, *,）的相关性，提出了 1O2 和 OP 之间的激基复合物的初始形成，其演化为两性离子过渡态。对一些反应产物进行了表征，其中得到了 3-甲基-甲基-5-(甲胺)-1,5-脱氢乙内酰脲作为 TMU 的主要光氧化产物。提出了形成该反应产物和其他反应产物的反应机制。