β-biliverdin-IX dimethyl ester

• 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: β-biliverdin-IX dimethyl ester
• 化学式: C₃₅H₃₈N₄O₆
• 分子量: 610.71
• InChiKey: IEIGGQKEJMEBIQ-WEWPOJETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.98
• 重原子数：
  45.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  138.95
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  β-biliverdin-IX dimethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 β-biliverdin-IX
  参考文献：
  名称：

  biliverdin-IX在人体中的尿液排泄。

  摘要：

  使用来自七个健康成年人的尿液样本研究了α-，β-，γ-和δ-胆小素-IX的四个异构体的分布和相对比例。将来自样品的联肝素吸附在滑石上，然后将吸附的联肝素浸入甲醇和浓硫酸的溶液中，以衍生为二甲基酯。将酯送入反相柱中进行纯化，然后在反相柱上通过HPLC进行定量。分析显示，在24小时尿液中的biliverdins由6.4 +/- 2.5 nmolα-和9.3 +/- 5.4 nmolβ-异构体组成。HPLC分析表明，δ-异构体的存在量要少得多，但没有检测到γ-异构体。α-和β-异构体的鉴定通过共色谱和吸收光谱进行。

  DOI：

  10.1248/bpb.18.481
• 作为产物：
  描述：

  甲醇 、 hemin 在 维生素 C 、 盐酸 作用下， 以 吡啶 、 aq. phosphate buffer 为溶剂， 反应 21.0h， 生成 3-[2-[(E)-[3-(3-甲氧基-3-氧代-丙基)-4-甲基-5-[(E)-(3-甲基-5-氧代-4-乙烯基-吡咯-2-亚基)甲基]吡咯-2-亚基]甲基]-4-甲基-5-[(E)-(4-甲基-5-氧代-3-乙烯基-吡咯-2-亚基)甲基]-1H-吡咯-3-基]丙酸甲酯 、 β-biliverdin-IX dimethyl ester 、 3,3'-(3,7,12,17-tetramethyl-1,19-dioxo-8,13-divinyl-1,19,22,24-tetrahydro-21H-biline-2,18-diyl)-bis-propionic acid dimethyl ester 、 methyl 3-[(2Z,5E)-5-[[3-ethenyl-5-[(Z)-(3-ethenyl-4-methyl-5-oxopyrrol-2-ylidene)methyl]-4-methyl-1H-pyrrol-2-yl]methylidene]-2-[[3-(3-methoxy-3-oxopropyl)-4-methyl-5-oxopyrrol-2-yl]methylidene]-4-methylpyrrol-3-yl]propanoate
  参考文献：
  名称：

  Heme-iron utilization by Leptospira interrogans requires a heme oxygenase and a plastidic-type ferredoxin-NADP+ reductase

  摘要：

  Background: Heme oxygenase catalyzes the conversion of heme to iron, carbon monoxide and biliverdin employing oxygen and reducing equivalents. This enzyme is essential for heme-iron utilization and contributes to virulence in Leptospira interrogans. Methods: A phylogenetic analysis was performed using heme oxygenases sequences from different organisms including saprophytic and pathogenic Leptospira species. L. interrogans heme oxygenase (LepHO) was cloned, overexpressed and purified. The structural and enzymatic properties of LepHO were analyzed by UV-vis spectrophotometry and (1)H NMR. Heme-degrading activity, ferrous iron release and biliverdin production were studied with different redox partners. Results: A plastidic type, high efficiently ferredoxin-NADP(+) reductase (LepFNR) provides the electrons for heme turnover by heme oxygenase in L. interrogans. This catalytic reaction does not require a ferredoxin. Moreover, LepFNR drives the heme degradation to completeness producing free iron and α-biliverdin as the final products. The phylogenetic divergence between heme oxygenases from saprophytic and pathogenic species supports the functional role of this enzyme in L. interrogans pathogenesis. Conclusions: Heme-iron scavenging by LepHO in L. interrogans requires only LepFNR as redox partner. Thus, we report a new substrate of ferredoxin-NADP(+) reductases different to ferredoxin and flavodoxin, the only recognized protein substrates of this flavoenzyme to date. The results presented here uncover a fundamental step of heme degradation in L. interrogans. General significance: Our findings contribute to understand the heme-iron utilization pathway in Leptospira. Since iron is required for pathogen survival and infectivity, heme degradation pathway may be relevant for therapeutic applications.

  DOI：

  10.1016/j.bbagen.2014.07.021

文献信息

• Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification
  作者：Yaoqiu Zhu、Dejan Nikolic、Richard B. Van Breemen、Richard B. Silverman

  DOI：10.1021/ja0445645

  日期：2005.1.1

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.