N-(2H3)乙酰半胱氨酸 | 131685-11-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 半胱氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-(2H3)乙酰半胱氨酸
• 中文别名: N-乙酰-D3-L-半胱氨酸
• 英文名称: N-[2H3]Acetylcysteine
• 英文别名: N-acetyl-L-cysteine-D3；N-(acetyl-d3)-L-cysteine；MAd3；(2R)-3-sulfanyl-2-[(2,2,2-trideuterioacetyl)amino]propanoic acid
• CAS: 131685-11-5
• 化学式: C₅H₉NO₃S
• 分子量: 166.174
• InChiKey: PWKSKIMOESPYIA-OSIBIXDNSA-N

物化性质

• 熔点：
  98-100°C
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微）、水（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.4
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 储存条件：
  -20°C 冰箱

制备方法与用途

乙酰半胱氨酸-d3（N-乙酰半胱氨酸-d3）是氘标记的乙酰半胱氨酸。乙酰半胱氨酸（N-乙酰半胱氨酸）是一种黏液溶解剂，能够减少黏液的厚度。作为一种活性氧抑制剂，它还能诱导细胞凋亡[1][2]。此外，乙酰半胱氨酸还具有抗流感病毒活性[7]。另外，作为半胱氨酸前体，它能通过中和依赖花生四烯酸的5-脂氧合酶活性产生的有毒脂质来预防氯化血红素诱导的铁死亡[5]。

反应信息

• 作为反应物：
  描述：

  4-羟基-2-壬烯酸 、 N-(2H3)乙酰半胱氨酸 以 乙醇 为溶剂， 反应 2.0h， 生成 HNA-MA-d3
  参考文献：
  名称：

  Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study

  摘要：

  The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects Currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.freeradbiomed.2009.10.025
• 作为产物：
  描述：

  N-(乙酰基-d3)-S-苄基-L-半胱氨酸 在 sodium 作用下， 以 氨 为溶剂， 以85%的产率得到N-(2H3)乙酰半胱氨酸
  参考文献：
  名称：

  Urinary Metabolite Profile of Phenyl and o-Cresyl Glycidyl Ether in Rats:  Identification of a Novel Pathway Leading to N-Acetylserine O-Conjugates

  摘要：

  The urinary excretion of metabolites of phenyl glycidyl ether (PGE) and o-cresyl glycidyl ether (o-CGE) was investigated in rats. Urine was collected, in fractions, from rats intraperitoneally administered PGE or o-CGE in doses ranging from 0.033 to 1.0 mmol/kg. The metabolites were extracted from acidified urine with ethyl acetate or diethyl ether, and their identity was elucidated by GC/MS analysis. The epoxide of PGE can be inactivated by glutathione (GSH) conjugation or epoxide hydrolysis. After further metabolism, these routes lead to the urinary excretion of phenyl glycidyl ether mercapturic acid (PGEMA) and 3-(phenyloxy)lactic acid (POLA). The excretion of PGEMA and POLA was described before and is confirmed in this study. Additionally, a new metabolite was identified as N-acetyl-O-phenylserine (NAPS), which is proposed to be formed from POLA by subsequent oxidation, transamination, and N-acetylation. For PGEMA a linear dose-excretion relationship was found (r(2) = 0.988), and the percentage of the dose excreted declined from 27 % to 10 % with increasing PGE dose. For NAPS also a linear dose-excretion relationship was found (r(2) = 0.985), and NAPS accounted for 27 % of the PGE dose. The excretion of PGEMA and NAPS was rather fast: 93 % and 75 %, respectively, of the respective total cumulative amounts excreted was already collected within 6 h after administration. The urinary metabolite profile of o-CGE was not investigated in rats before. Three urinary metabolites of o-CGE were identified, namely, 3-(o-cresyloxy)lactic acid (COLA), o-cresyl glycidyl ether mercapturic acid (o-CGEMA), and N-acetyl-O-(o-cresyl)serine (NAGS), showing that the metabolite profiles of PGE and o-CGE are comparable. Up to a o-CGE dose of 0.333 mmol/kg, the excretion of o-CGEMA was linear (r(2) = 0.997), while above this dose the excretion did not increase anymore. The percentage of the o-CGE dose excreted as o-CGEMA declined from 31 % to 11 % with increasing dose. Again 93 % of the total cumulative amount of o-CGEMA excreted was collected within 6 h after administration of o-CGE. Analytical methods were developed for the quantitative determination of mercapturic acid metabolites of PGE and o-CGE. These methods were sufficiently sensitive for their determination in urine of rats administered PGE or o-CGE in the dose range applied. It is anticipated that the analytical methods developed are also sufficiently sensitive to investigate excretion of the mercapturic acid metabolites in humans occupationally exposed to low air concentrations (< 6 mg/m(3) of air, 8h-TWA) of PGE or o-CGE.

  DOI：

  10.1021/tx970020n

文献信息

• Urinary Metabolite Profile of Phenyl and <i>o</i>-Cresyl Glycidyl Ether in Rats:  Identification of a Novel Pathway Leading to <i>N</i>-Acetylserine O-Conjugates
  作者：Ben M. de Rooij、Jan N. M. Commandeur、John W. Hommes、Tom Aalbers、Ed J. Groot、Nico P. E. Vermeulen

  DOI：10.1021/tx970020n

  日期：1998.2.1

  The urinary excretion of metabolites of phenyl glycidyl ether (PGE) and o-cresyl glycidyl ether (o-CGE) was investigated in rats. Urine was collected, in fractions, from rats intraperitoneally administered PGE or o-CGE in doses ranging from 0.033 to 1.0 mmol/kg. The metabolites were extracted from acidified urine with ethyl acetate or diethyl ether, and their identity was elucidated by GC/MS analysis. The epoxide of PGE can be inactivated by glutathione (GSH) conjugation or epoxide hydrolysis. After further metabolism, these routes lead to the urinary excretion of phenyl glycidyl ether mercapturic acid (PGEMA) and 3-(phenyloxy)lactic acid (POLA). The excretion of PGEMA and POLA was described before and is confirmed in this study. Additionally, a new metabolite was identified as N-acetyl-O-phenylserine (NAPS), which is proposed to be formed from POLA by subsequent oxidation, transamination, and N-acetylation. For PGEMA a linear dose-excretion relationship was found (r(2) = 0.988), and the percentage of the dose excreted declined from 27 % to 10 % with increasing PGE dose. For NAPS also a linear dose-excretion relationship was found (r(2) = 0.985), and NAPS accounted for 27 % of the PGE dose. The excretion of PGEMA and NAPS was rather fast: 93 % and 75 %, respectively, of the respective total cumulative amounts excreted was already collected within 6 h after administration. The urinary metabolite profile of o-CGE was not investigated in rats before. Three urinary metabolites of o-CGE were identified, namely, 3-(o-cresyloxy)lactic acid (COLA), o-cresyl glycidyl ether mercapturic acid (o-CGEMA), and N-acetyl-O-(o-cresyl)serine (NAGS), showing that the metabolite profiles of PGE and o-CGE are comparable. Up to a o-CGE dose of 0.333 mmol/kg, the excretion of o-CGEMA was linear (r(2) = 0.997), while above this dose the excretion did not increase anymore. The percentage of the o-CGE dose excreted as o-CGEMA declined from 31 % to 11 % with increasing dose. Again 93 % of the total cumulative amount of o-CGEMA excreted was collected within 6 h after administration of o-CGE. Analytical methods were developed for the quantitative determination of mercapturic acid metabolites of PGE and o-CGE. These methods were sufficiently sensitive for their determination in urine of rats administered PGE or o-CGE in the dose range applied. It is anticipated that the analytical methods developed are also sufficiently sensitive to investigate excretion of the mercapturic acid metabolites in humans occupationally exposed to low air concentrations (< 6 mg/m(3) of air, 8h-TWA) of PGE or o-CGE.
• Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study
  作者：Heather C. Kuiper、Brandi L. Langsdorf、Cristobal L. Miranda、Jacqueline Joss、Carole Jubert、John E. Mata、Jan F. Stevens

  DOI：10.1016/j.freeradbiomed.2009.10.025

  日期：2010.1

  The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects Currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress. (C) 2009 Elsevier Inc. All rights reserved.