propionyl-CoA | 317-66-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: propionyl-CoA
• 英文别名: S-[2-[3-[[4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] propanethioate
• CAS: 317-66-8
• 化学式: C₂₄H₄₀N₇O₁₇P₃S
• 分子量: 823.606
• InChiKey: QAQREVBBADEHPA-UXYNFSPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  52
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  389
• 氢给体数：
  9
• 氢受体数：
  22

ADMET

代谢

有机磷化合物的代谢主要通过氧化、通过酯酶的水解以及与谷胱甘肽的反应进行。去甲基化和葡萄糖苷酸化也可能发生。有机磷农药的氧化可能导致产生中等毒性的产物。一般来说，磷硫代酸盐本身并不直接有毒，但需要经过氧化代谢转化为近端毒素。谷胱甘肽转移酶反应产生的产物在大多数情况下毒性较低。对氧磷酶（PON1）是有机磷化合物代谢中的关键酶。PON1可以通过水解使一些有机磷化合物失活。PON1水解多种有机磷杀虫剂以及神经毒剂（如梭曼、沙林和VX）的活性代谢物。PON1的多态性导致这种酯酶的酶水平和催化效率不同，这反过来表明不同个体可能更容易受到有机磷暴露的毒性影响。

Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

在丙酸尿症中，丙酰辅酶A在线粒体内大量积累；然后游离肉碱被酯化，形成丙酰肉碱，随后通过尿液排出。由于饮食和合成中的肉碱供应有限，这类患者很容易因为酰基肉碱衍生物的丢失增加而发展成肉碱缺乏症。

In propionic aciduria, propionyl CoA accumulates within the mitochondria in massive quantities; free carnitine is then esterified, creating propionyl carnitine, which is then excreted in the urine. Because the supply of carnitine in the diet and from synthesis is limited, such patients readily develop carnitine deficiency as a result of the increased loss of acylcarnitine derivatives.

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

丙酸血症在新生儿早期表现为进行性脑病。由于继发性高氨血症、感染、心肌病或基底节区中风，死亡可能会迅速发生。（维基百科）

Propionic acidemia presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke. (Wikipedia)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

丙酸血症在新生儿出生后几乎立即表现出特征。症状包括进食困难、呕吐、脱水、酸中毒、肌肉张力低（低张力）、癫痫和乏力。丙酸血症的影响很快就会变得危及生命。（维基百科）

Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening. (Wikipedia)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

丙酸尿症相关的肉碱缺乏需要补充游离肉碱，以超出正常饮食摄入量，以继续清除（解毒）积累的有机酸。

The carnitine deficiency associated with propionic acuduria demands supplementation of free carnitine above the normal dietary intake to continue to remove (detoxify) the accumulating organic acids.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  propionyl-CoA 、 urauchimycin B 在 Streptomyces albus J₁₀₇₄ AntB 作用下， 反应 2.0h， 生成 urauchimycin B
  参考文献：
  名称：

  Characterization of AntB, a Promiscuous Acyltransferase Involved in Antimycin Biosynthesis

  摘要：

  The in vivo and in vitro characterization of AntB, a dedicated acyltransferase encoded in the antimycin biosynthetic gene cluster, which catalyzes the C-8 acyloxy formation is reported. It is demonstrated that AntB has broad substrate specificity toward both the acyl substrate and the acyl carrier and produces more antimycin analogues with varying C-8 acyloxy moieties.

  DOI：

  10.1021/ol4014365
• 作为产物：
  描述：

  coenzyme A 、 S-碘化丙酰硫代胆碱 生成 propionyl-CoA
  参考文献：
  名称：

  OUYANG, TIANMEI;WALT, DAVID R., J. ORG. CHEM., 56,(1991) N1, C. 3752-3755

  摘要：

  DOI：

文献信息

• OUYANG, TIANMEI;WALT, DAVID R., J. ORG. CHEM., 56,(1991) N1, C. 3752-3755
  作者：OUYANG, TIANMEI、WALT, DAVID R.

  DOI：——

  日期：——
• Characterization of AntB, a Promiscuous Acyltransferase Involved in Antimycin Biosynthesis
  作者：Moriah Sandy、Xuejun Zhu、Zhe Rui、Wenjun Zhang

  DOI：10.1021/ol4014365

  日期：2013.7.5

  The in vivo and in vitro characterization of AntB, a dedicated acyltransferase encoded in the antimycin biosynthetic gene cluster, which catalyzes the C-8 acyloxy formation is reported. It is demonstrated that AntB has broad substrate specificity toward both the acyl substrate and the acyl carrier and produces more antimycin analogues with varying C-8 acyloxy moieties.