γ-hydroxybutyrate | 692-28-4

• 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: γ-hydroxybutyrate
• 英文别名: gamma-hydroxybutyrate；4-hydroxybutyrate；GHB；JZP-258；4-Hydroxybutanoate
• CAS: 692-28-4
• 化学式: C₄H₇O₃
• 分子量: 103.098
• InChiKey: SJZRECIVHVDYJC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

消除途径：动物研究表明，代谢是消除氧酸的主要途径，通过三羧酸（克雷布斯）循环和次要的β-氧化产生二氧化碳和水。琥珀酸进入克雷布斯循环，在那里它被代谢成二氧化碳和水。粪便和肾排泄可以忽略不计。 5%肾排泄。 半衰期：30至60分钟

Route of Elimination: Animal studies indicate that metabolism is the major elimination pathway for sodium oxybate, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water. Fecal and renal excretion is negligible. 5% renal elimination. Half Life: 30 to 60 minutes

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

γ-羟基丁酸（GHB）在大脑中的浓度要高得多，并激活GABAB受体，这些受体主要对其镇静效果负责。GHB受体在大脑的许多区域密集表达，包括皮层和海马体，GHB对这些受体的亲和力最高。对GHB受体的研究相对有限；然而，有证据表明，在某些大脑区域激活GHB受体会导致谷氨酸的释放，谷氨酸是主要的兴奋性神经递质。 激活GHB受体和GABA(B)是GHB成瘾特征的原因。GHB对多巴胺释放的影响是双相的，[19]低浓度通过GHB受体刺激多巴胺释放。[20]高浓度通过GABA(B)受体抑制多巴胺释放，其他GABA(B)激动剂如巴氯芬和芬尼布特也是如此。[21]在最初的抑制阶段之后，多巴胺释放然后通过GHB受体增加。这解释了GHB的镇静和刺激性质的矛盾混合，以及所谓的“反跳”效应，使用GHB作为睡眠剂的个体在GHB诱导的深度睡眠几小时后突然醒来。也就是说，随着时间的推移，系统中的GHB浓度降低到低于显著激活GABAB受体的阈值，主要激活GHB受体，导致清醒。

GHB reaches much higher concentrations in the brain and activates GABAB receptors, which are primarily responsible for its sedative effects. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter. Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic,[19] low concentrations stimulate dopamine release via the GHB receptor.[20] Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut.[21] After an initial phase of inhibition, dopamine release is then increased via the GHB receptor. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant GABAB receptor activation and activates predominantly the GHB receptor, leading to wakefulness.

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

长期高水平的4-羟基丁酸与称为4-羟基丁酸尿症/琥珀酸半醛脱氢酶缺乏的遗传代谢错误有关。

Chronically high levels of 4-hydroxybutyric acid are associated with the inborn errors of metabolism called: 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency.

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  2-氧代-戊二酸离子(2-) 、 γ-hydroxybutyrate 生成 (2R)-2-hydroxyglutarate 、 4-Oxobutanoate
  参考文献：
  名称：

  人羟酸-氧酸转氢酶的动力学表征：与D-2-羟基戊二酸和γ-羟基丁酸尿症的相关性。

  摘要：

  我们研究了羟酸-草酸转氢酶（HOT）的存在，该酶可催化不依赖辅因子的γ-羟基丁酸酯（GHB）转化为琥珀酸半醛，再将2-酮戊二酸（2-KG）还原为D-2-羟基戊二酸（D （-2-HG），以[2H6] GHB和2-KG为底物在人肝提取物中。我们使用GC-MS分析测量了D- [2H] 2-HG中2H的掺入，为人类的HOT活性提供了证据。HOT的动力学表征是在正向和反向进行的。为了研究来自D-2-羟基戊二酸尿症患者的培养人成纤维细胞的HOT活性测定，我们使用了[2H6] GHB和[2H4] 2-KG作为共底物。在该系统中，通过测量D- [2H5] 2-HG的产生来量化HOT活性。D-2-羟基戊二酸尿症患者的成纤维细胞显示出正常的HOT活性。我们的结果提供了人类组织中HOT活性的首次证明和初步动力学表征。

  DOI：

  10.1007/s10545-005-0114-x
• 作为产物：
  描述：

  γ-丁内酯 在 potassium chloride 、 hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 γ-hydroxybutyrate
  参考文献：
  名称：

  Barton, Patrick; Laws, Andrew P.; Page, Michael I., Journal of the Chemical Society. Perkin transactions II, 1994, # 9, p. 2021 - 2030

  摘要：

  DOI：

文献信息

• COPOLYMER COMPRISING 4-HYDROXYBUTYRATE UNIT AND LACTATE UNIT AND ITS MANUFACTURING METHOD
  申请人：Park Si-Jae

  公开号：US20100222545A1

  公开（公告）日：2010-09-02

  The present invention relates to a copolymer comprising 4-hydroxybutyrate monomer unit and lactate monomer unit, a copolymer 4-hydroxybutyrate monomer unit, lactate monomer unit and 3-hydroxyalkanoate, or their preparing method. More specifically, the present invention relates to a method for preparing a copolymer comprising lactate monomer; 4-hydroxybutyrate monomer; and optionally 3-hydroxyalkanoate, wherein the method comprises culturing a cell or plant comprising the gene of enzyme converting lactate and 3-hydroxyalkanoate into lactyl-CoA and 3-hydroxyalkanoyl-CoA, respectively, phosphotransbutylase gene, butyrate kinase gene and polyhydroxyalkanoate synthase gene together, and the copolymer made by the method. The copolymer of the present invention is a biodegradable polymer being able to be usefully used instead of conventional synthetic plastic, and the copolymer can be used for medical use.

  本发明涉及一种共聚物，其包含4-羟基丁酸单体单元和乳酸单体单元，或者包含4-羟基丁酸单体单元、乳酸单体单元和3-羟基烷酸单体单元的共聚物，以及它们的制备方法。更具体地说，本发明涉及一种制备包含乳酸单体单元、4-羟基丁酸单体单元和可选的3-羟基烷酸单体单元的共聚物的方法，其中该方法包括培养含有将乳酸和3-羟基烷酸转化为乳酰辅酶A和3-羟基烷酰辅酶A的酶基因、磷酸丁醇转移酶基因、丁酸激酶基因和聚羟基烷酸合酶基因的细胞或植物，并由该方法制备的共聚物。本发明的共聚物是一种可生物降解的聚合物，能够代替传统的合成塑料有用地使用，可用于医疗用途。
• Copolymer comprising 4-hydroxybutyrate unit and lactate unit and its manufacturing method
  申请人：Park Si-Jae

  公开号：US08383379B2

  公开（公告）日：2013-02-26

  The present invention relates to a copolymer comprising 4-hydroxybutyrate monomer unit and lactate monomer unit, a copolymer 4-hydroxybutyrate monomer unit, lactate monomer unit and 3-hydroxyalkanoate, or their preparing method. More specifically, the present invention relates to a method for preparing a copolymer comprising lactate monomer; 4-hydroxybutyrate monomer; and optionally 3-hydroxyalkanoate, wherein the method comprises culturing a cell or plant comprising the gene of enzyme converting lactate and 3-hydroxyalkanoate into lactyl-CoA and 3-hydroxyalkanoyl-CoA, respectively, phosphotransbutylase gene, butyrate kinase gene and polyhydroxyalkanoate synthase gene together, and the copolymer made by the method. The copolymer of the present invention is a biodegradable polymer being able to be usefully used instead of conventional synthetic plastic, and the copolymer can be used for medical use.

  本发明涉及一种共聚物，包括4-羟基丁酸单体单元和乳酸单体单元，一种共聚物4-羟基丁酸单体单元，乳酸单体单元和3-羟基烷酸单体单元，或其制备方法。更具体地，本发明涉及一种制备包括乳酸单体单元；4-羟基丁酸单体单元；以及可选的3-羟基烷酸单体单元的共聚物的方法，其中该方法包括培养包含将乳酸和3-羟基烷酸转化为乳酰辅酶A和3-羟基烷酰辅酶A的酶基因，磷酸丁酰转移酶基因，丁酸激酶基因和聚羟基烷酸合成酶基因的细胞或植物，并通过该方法制备的共聚物。本发明的共聚物是一种可生物降解的聚合物，可以代替传统的合成塑料有用地使用，并可用于医疗用途。
• Kinetics aspects of Gamma-hydroxybutyrate dehydrogenase
  作者：Esther S. Taxon、Lila P. Halbers、Stanley M. Parsons

  DOI：10.1016/j.bbapap.2020.140376

  日期：2020.5

  metabolically related enzymes, the Group III family of Fe2+-dependent alcohol dehydrogenases (ADHs) and the separate subfamily of nucleoside diphosphates linked to x (nudix) hydrolases that activate Group III ADHs are under-characterized. Here we report the steady-state initial-velocity forward direction (alcohol → aldehyde) reaction of a Group III ADH, namely gamma-hydroxybutyrate dehydrogenase (GHBDH, UniProt:

  两组代谢相关的酶，Fe 2+依赖性酒精脱氢酶（ADHs）的III组家族和与激活III组ADH的x（nudix）水解酶连接的核苷二磷酸的单独亚家族，功能不足。在这里，我们报道了从Cupriavidus necator克隆为融合蛋白的III组ADH，即γ-羟基丁酸脱氢酶（GHBDH，UniProt：Q59104）的稳态初始速度正向反应（酒精→醛）。我们还报告了Nudix水解酶对GHBDH反应的影响。在最佳pH 9.0时，GHBDH反应被两种不同的饱和纯化nudix水解酶活化约2倍，即甲醇芽孢杆菌活化剂（ACT，UniProt：I3EA59）和大肠杆菌NudF（UniProt Q93K97）蛋白。在约7.0的生理pH值下，ACT活化> 3.5倍。在两种情况下，正向未活化反应和ACT活化反应的pH值9.0的初始速率表征均显示出琥珀酸半醛对GHB的竞争性抑制作用，以及其他三种底物-产物组合的非竞争性抑制作用。这种模式与Mono-Iso
• Identification of Missing Genes and Enzymes for Autotrophic Carbon Fixation in <i>Crenarchaeota</i>
  作者：W. Hugo Ramos-Vera、Michael Weiss、Eric Strittmatter、Daniel Kockelkorn、Georg Fuchs

  DOI：10.1128/jb.01156-10

  日期：2011.3

  Two autotrophic carbon fixation cycles have been identified in Crenarchaeota . The dicarboxylate/4-hydroxybutyrate cycle functions in anaerobic or microaerobic autotrophic members of the Thermoproteales and Desulfurococcales . The 3-hydroxypropionate/4-hydroxybutyrate cycle occurs in aerobic autotrophic Sulfolobales ; a similar cycle may operate in autotrophic aerobic marine Crenarchaeota . Both cycles form succinyl-coenzyme A (CoA) from acetyl-CoA and two molecules of inorganic carbon, but they use different means. Both cycles have in common the (re)generation of acetyl-CoA from succinyl-CoA via identical intermediates. Here, we identified several missing enzymes/genes involved in the seven-step conversion of succinyl-CoA to two molecules of acetyl-CoA in Thermoproteus neutrophilus ( Thermoproteales ), Ignicoccus hospitalis ( Desulfurococcales ), and Metallosphaera sedula ( Sulfolobales ). The identified enzymes/genes include succinyl-CoA reductase, succinic semialdehyde reductase, 4-hydroxybutyrate-CoA ligase, bifunctional crotonyl-CoA hydratase/( S )-3-hydroxybutyryl-CoA dehydrogenase, and beta-ketothiolase. 4-Hydroxybutyryl-CoA dehydratase, which catalyzes a mechanistically intriguing elimination of water, is well conserved and rightly can be considered the key enzyme of these two cycles. In contrast, several of the other enzymes evolved from quite different sources, making functional predictions based solely on genome interpretation difficult, if not questionable.

  摘要 目前已在芸苔菌中发现两种自养碳固定循环 自养碳固定循环 .二羧酸盐/4-羟基丁酸盐循环在厌氧或微氧自养成员中起作用。 热蛋白 和 脱硫球菌纲 .3-羟基丙酸盐/4-羟基丁酸盐循环出现在好氧自养型的 硫醇杆菌 ；类似的循环可能在自养好氧的海洋 Crenarchaeota .这两个循环都从乙酰-CoA 和两分子无机碳中生成琥珀酰辅酶 A (CoA)，但使用的方式不同。这两种循环的共同点都是通过相同的中间产物从琥珀酰-CoA（再）生成乙酰-CoA。在这里，我们发现了几种缺失的酶/基因，它们参与了琥珀酰-CoA 向两分子乙酰-CoA 的七步转化过程。 中性热保护菌 ( 热蛋白 ), 医院球菌 ( 去硫球菌属 ）和 金属磷藻 ( Sulfolobales ).确定的酶/基因包括琥珀酰-CoA 还原酶、琥珀酰半醛还原酶、4-羟基丁酸-CoA 连接酶、双功能巴豆酰-CoA 水合酶/( S )-3-羟基丁酰-CoA 脱氢酶和 beta-酮硫醇酶。4-hydroxybutyryl-CoA 脱水酶催化的水消除机制非常有趣，它保存完好，可被视为这两个循环的关键酶。相比之下，其他几种酶的进化来源却大相径庭，因此仅根据基因组解读来预测其功能是很困难的，甚至是值得怀疑的。
• Malonic Semialdehyde Reductase, Succinic Semialdehyde Reductase, and Succinyl-Coenzyme A Reductase from <i>Metallosphaera sedula</i> : Enzymes of the Autotrophic 3-Hydroxypropionate/4-Hydroxybutyrate Cycle in <i>Sulfolobales</i>
  作者：Daniel Kockelkorn、Georg Fuchs

  DOI：10.1128/jb.00794-09

  日期：2009.10.15

  A 3-hydroxypropionate/4-hydroxybutyrate cycle operates during autotrophic CO ₂ fixation in various members of the Crenarchaea . In this cycle, as determined using Metallosphaera sedula , malonyl-coenzyme A (malonyl-CoA) and succinyl-CoA are reductively converted via their semialdehydes to the corresponding alcohols 3-hydroxypropionate and 4-hydroxybutyrate. Here three missing oxidoreductases of this cycle were purified from M. sedula and studied. Malonic semialdehyde reductase, a member of the 3-hydroxyacyl-CoA dehydrogenase family, reduces malonic semialdehyde with NADPH to 3-hydroxypropionate. The latter compound is converted via propionyl-CoA to succinyl-CoA. Succinyl-CoA reduction to succinic semialdehyde is catalyzed by malonyl-CoA/succinyl-CoA reductase, a promiscuous NADPH-dependent enzyme that is a paralogue of aspartate semialdehyde dehydrogenase. Succinic semialdehyde is then reduced with NADPH to 4-hydroxybutyrate by succinic semialdehyde reductase, an enzyme belonging to the Zn-dependent alcohol dehydrogenase family. Genes highly similar to the Metallosphaera genes were found in other members of the Sulfolobales . Only distantly related genes were found in the genomes of autotrophic marine Crenarchaeota that may use a similar cycle in autotrophic carbon fixation.

  摘要 3-羟基丙酸盐/4-羟基丁酸盐循环在自养型 CO 2 固定过程中，3-羟基丙酸 Crenarchaea .在这一循环中，利用 金属磷藻 中，丙二酰辅酶 A（丙二酰-CoA）和琥珀酰-CoA 通过半醛还原转化为相应的醇 3-羟基丙酸酯和 4-羟基丁酸酯。在此，我们从沉睡藻中纯化出了该循环中缺少的三种氧化还原酶。 M. sedula 并对其进行了研究。丙二酸半醛还原酶是 3-hydroxyacyl-CoA dehydrogenase 家族的成员，通过 NADPH 将丙二酸半醛还原成 3-hydroxypropionate 。后者通过丙酰-CoA 转化为琥珀酰-CoA。琥珀酰-CoA 还原成琥珀酸半醛的过程由丙二酰-CoA/琥珀酰-CoA 还原酶催化，这是一种依赖 NADPH 的杂合酶，是天冬氨酸半醛脱氢酶的旁系亲属。然后，琥珀酸半醛在 NADPH 的作用下被琥珀酸半醛还原酶还原成 4-羟基丁酸，该酶属于 Zn 依赖性醇脱氢酶家族。与 Metallosphaera 基因高度相似。 Sulfolobales .在自养型海洋生物 Crenarchaeota 的基因组中，只发现了与 Metallosphaera 基因高度相似的基因。 Crenarchaeota 可能在自养碳固定过程中使用了类似的循环。

表征谱图