harderoporphyrinogen | 42607-18-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: harderoporphyrinogen
• 英文别名: 12-ethenyl-5,10,15,20,22,24-hexahydro-3,8,13,17-tetramethyl-21H,23H-Porphine-2,7,18-tripropanoic acid；3-[13,17-bis(2-carboxyethyl)-7-ethenyl-3,8,12,18-tetramethyl-5,10,15,20,21,22,23,24-octahydroporphyrin-2-yl]propanoic acid
• CAS: 42607-18-1
• 化学式: C₃₅H₄₂N₄O₆
• 分子量: 614.742
• InChiKey: NJOHCPMVGKOWTE-UHFFFAOYSA-N

物化性质

• 沸点：
  916.8±65.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  175
• 氢给体数：
  7
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  harderoporphyrinogen 在 双氧水 作用下， 生成 3-vinyl-2,7,12,18-tetramethylporphyrin-8,13,17-tripropionic acid
  参考文献：
  名称：

  再次探讨厌氧性原卟啉原Ⅲ氧化酶HemN的机制。

  摘要：

  HemN是自由基S-腺苷升蛋氨酸（SAM）酶催化卟啉原III的氧化脱羧反应，从而产生原卟啉原IX，这是血红素生物合成的中间体。HemN在活性位点结合了两个SAM分子，但是如何利用这两个SAM来使原卟啉原III的两个丙酸酯基团依次脱羧仍然很困难。这里提供的证据表明，在HemN催化中，SAM充当氢继电器，介导基于自由基的氢从丙酸酯转移到活性位点中另一SAM生成的5'-脱氧腺苷（dAdo）自由基。还观察到意外的分流产物，这是由于单脱羧化中间体硬质卟啉原的乙烯基部分捕获了基于SAM的亚甲基基团而引起的。

  DOI：

  10.1002/anie.201814708
• 作为产物：
  描述：

  3-{5-Formyl-2-[5-formyl-3-(2-methoxycarbonyl-ethyl)-4-methyl-1H-pyrrol-2-ylmethyl]-4-methyl-1H-pyrrol-3-yl}-propionic acid methyl ester 在 盐酸 、 sodium amalgam 、 potassium tert-butylate 、 zinc diacetate 、 水 、 对甲苯磺酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 134.08h， 生成 harderoporphyrinogen
  参考文献：
  名称：

  不依赖于氧的粪卟啉原 III 氧化酶 HemN 在粪卟啉原 III 向原卟啉原 IX 的转化过程中利用硬卟啉原作为反应中间体

  摘要：

  摘要 在血红素生物合成过程中，不依赖氧的粪卟啉原 III 氧化酶 HemN 催化粪卟啉原 III 的 A 环和 B 环上的两个丙酸侧链氧化脱羧为相应的乙烯基，生成原卟啉原 IX。在这里，研究了 HemN 催化过程中两个脱羧步骤的顺序。通过HPLC分析分离出具有HemN活性的反应中间体，并通过质谱法鉴定为单乙烯基三丙酸卟啉。这种单乙烯基反应中间体在 HPLC 分析过程中表现出与硬卟啉（3-乙烯基-8,13,17-三丙酸-2,7,12,18-四甲基卟啉）相同的色谱行为。此外，HemN 能够利用化学合成的硬卟啉原作为底物并将其转化为原卟啉原 IX。

  DOI：

  10.1515/bc.2010.006

文献信息

• Direct Assay of Enzymes in Heme Biosynthesis for the Detection of Porphyrias by Tandem Mass Spectrometry. Uroporphyrinogen Decarboxylase and Coproporphyrinogen III Oxidase
  作者：Yuesong Wang、Paula Gatti、Martin Sadílek、C. Ronald Scott、František Tureček、Michael H. Gelb

  DOI：10.1021/ac702130n

  日期：2008.4.1

  We report new assays of enzymes uroporphyrinogen decarboxylase (UROD) and coproporphyrinogen III oxidase (CPO) in the heme biosynthetic pathway. The assays were developed for use in clinical diagnostics of inherited disorders porphyria cutanea tarda and hereditary coproporphyria, respectively. Electrospray ionization tandem mass spectrometry is used to monitor the decarboxylation of pentaporphyrinogen I or uroporphyrinogen III catalyzed by UROD and to determine the enzyme activity in human erythrocytes by measuring the production of coproporphyrinogen I or III. The Km value for pentaporphyrinogen I was measured as 0.17 ± 0.03 μM. A mass spectrometric assay was also developed for the two-step decarboxylative oxidation of coproporphyrinogen III to protoporphyrinogen IX catalyzed by CPO in mitochondria from human lymphocytes (Km = 0.066 ± 0.009 μM). The assays show good reproducibility, use simple workup by liquid−liquid extraction of enzymatic products, and employ commercially available substrates and internal standards.

  我们报告了血红素生物合成途径中尿卟啉原脱羧酶（UROD）和共卟啉原 III 氧化酶（CPO）的新测定方法。所开发的检测方法分别用于遗传性皮肤卟啉症和遗传性共卟啉症的临床诊断。电喷雾离子化串联质谱法用于监测由 UROD 催化的五卟啉原 I 或尿卟啉原 III 的脱羧过程，并通过测定共卟啉原 I 或 III 的生成量来确定人红细胞中酶的活性。经测定，五卟啉原 I 的 Km 值为 0.17 ± 0.03 μM。此外，还开发了一种质谱测定法，用于测定人淋巴细胞线粒体中 CPO 催化的共卟啉原 III 到原卟啉原 IX 的两步脱羧氧化反应（Km = 0.066 ± 0.009 μM）。这些检测方法具有良好的重现性，通过液-液萃取酶产物进行简单的处理，并采用市售底物和内标。
• Normal and Abnormal Heme Biosynthesis. 6. Synthesis and Metabolism of a Series of Monovinylporphyrinogens Related to Harderoporphyrinogen. Further Insights into the Oxidative Decarboxylation of Porphyrinogen Substrates by Coproporphyrinogen Oxidase
  作者：Timothy D. Lash、Ukti N. Mani、Anna-Sigrid I. M. Keck、Marjorie A. Jones

  DOI：10.1021/jo100083t

  日期：2010.5.21

  A series of vinylporphyrinogens were prepared to probe the enzyme coproporphyrinogen oxidase (CPO). Six (2-chloroethyl)porphyrins were synthesized from a common dipyrrylmethane via a,c-biladiene intermediates in excellent yields. Subsequent dehydrohalogenation with DBU in refluxing DMF then gave the required vinylporphyrin methyl esters, including harderoporphyrin-I, harderoporphyrin-III, and isoharderoporphyrin

  制备了一系列乙烯基卟啉原，以探测酶原卟啉原氧化酶（CPO）。从常见的二吡咯甲烷经a，c合成六种（2-氯乙基）卟啉-biladiene中间体，产率极高。随后在回流的DMF中用DBU进行脱卤化氢，得到所需的乙烯基卟啉甲酯，包括硬卟啉-I，硬卟啉-III和异硬卟啉。将相应的卟啉原羧酸与含有CPO酶的鸡红细胞裂解液一起孵育，并分析产物。硬质卟啉原III的17-乙基类似物，而不是其13-乙基异构体，被证明是CPO的优良底物，符合该酶活性位点的拟议模型。另外，显示出硬卟啉原-VII，即协同原卟啉原-IV代谢中的单乙烯基中间体，是该酶的同样良好的底物。但是，异硬质卟啉原缺乏外围取代基的正确顺序，也是CPO的底物。此外，显示出硬质卟啉原的非天然I型异构体可被CPO作用，但在这种情况下，可观察到进一步的代谢，从而提供了前所未有的三乙烯基卟啉原产物。分离出相应的卟啉甲酯，并通过FAB MS和质子NMR光谱进行
• Metabolism of pentacarboxylate porphyrinogens by highly purified human coproporphyrinogen oxidase: Further evidence for the existence of an abnormal pathway for heme biosynthesis
  作者：Christopher L. Cooper、Christian M. Stob、Marjorie A. Jones、Timothy D. Lash

  DOI：10.1016/j.bmc.2005.06.051

  日期：2005.11

  An abnormal series of porphyrin tetracarboxylic acids known as the isocoproporphyrins, are commonly excreted by patients suffering from the disease porphyria cutanea tarda (PCT). These porphyrins appear to arise by bacterial degradation of dehydroisocoproporphyrinogen that is generated by the premature metabolism of the normal pentacarboxylate intermediate (5dab) by coproporphyrinogen oxidase (copro'gen oxidase). This porphyrinogen can be further metabolized by uroporphyrinogen decarboxylase to give harderoporphyrinogen, one of the usual intermediates in heme biosynthesis. Therefore, it is possible that some of the heme formed under abnormal conditions may originate from the 'isocopro-type' porphyrinogen intermediate. In order to investigate the feasibility of alternative pathways for heme biosynthesis, the four type III pentacarboxylate isomeric porphyrinogens were incubated with purified, cloned human copro'gen oxidase at 37 degrees C with various substrate concentrations under initial velocity conditions. Of the four isomers, only 5dab was a substrate for copro'gen oxidase and this gave dehydroisocoproporphyrin. The structure of the related porphyrin tetrarnethyl ester was confirmed by proton NMR spectroscopy and mass spectrometry. The Km value for proto'gen-IX formation from copro'gen, an indicator of molecular recognition, was similar to the K-m value for monovinyl product formation with 5dab, although copro'gen-III has an approximately twofold higher K-cat value. Although 5dab is a slightly poorer substrate than copro'gen-111, these results support the hypothesis that an abnormal route for heme biosynthesis is possible in humans suffering from PCT or related syndromes such as hexachlorobenzene poisoning. (c) 2005 Elsevier Ltd. All rights reserved.
• The oxygen-independent coproporphyrinogen III oxidase HemN utilizes harderoporphyrinogen as a reaction intermediate during conversion of coproporphyrinogen III to protoporphyrinogen IX
  作者：Katrin Rand、Claudia Noll、Hans Martin Schiebel、Dorit Kemken、Thomas Dülcks、Markus Kalesse、Dirk W. Heinz、Gunhild Layer

  DOI：10.1515/bc.2010.006

  日期：2010.1.1

  Abstract During heme biosynthesis the oxygen-independent coproporphyrinogen III oxidase HemN catalyzes the oxidative decarboxylation of the two propionate side chains on rings A and B of coproporphyrinogen III to the corresponding vinyl groups to yield protoporphyrinogen IX. Here, the sequence of the two decarboxylation steps during HemN catalysis was investigated. A reaction intermediate of HemN activity

  摘要 在血红素生物合成过程中，不依赖氧的粪卟啉原 III 氧化酶 HemN 催化粪卟啉原 III 的 A 环和 B 环上的两个丙酸侧链氧化脱羧为相应的乙烯基，生成原卟啉原 IX。在这里，研究了 HemN 催化过程中两个脱羧步骤的顺序。通过HPLC分析分离出具有HemN活性的反应中间体，并通过质谱法鉴定为单乙烯基三丙酸卟啉。这种单乙烯基反应中间体在 HPLC 分析过程中表现出与硬卟啉（3-乙烯基-8,13,17-三丙酸-2,7,12,18-四甲基卟啉）相同的色谱行为。此外，HemN 能够利用化学合成的硬卟啉原作为底物并将其转化为原卟啉原 IX。
• Revisiting the Mechanism of the Anaerobic Coproporphyrinogen III Oxidase HemN
  作者：Xinjian Ji、Tianlu Mo、Wan‐Qiu Liu、Wei Ding、Zixin Deng、Qi Zhang

  DOI：10.1002/anie.201814708

  日期：2019.5.6

  HemN is a radical S‐adenosyl‐l‐methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Provided

  HemN是自由基S-腺苷升蛋氨酸（SAM）酶催化卟啉原III的氧化脱羧反应，从而产生原卟啉原IX，这是血红素生物合成的中间体。HemN在活性位点结合了两个SAM分子，但是如何利用这两个SAM来使原卟啉原III的两个丙酸酯基团依次脱羧仍然很困难。这里提供的证据表明，在HemN催化中，SAM充当氢继电器，介导基于自由基的氢从丙酸酯转移到活性位点中另一SAM生成的5'-脱氧腺苷（dAdo）自由基。还观察到意外的分流产物，这是由于单脱羧化中间体硬质卟啉原的乙烯基部分捕获了基于SAM的亚甲基基团而引起的。