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γ-羟基丁酸在体外转化为γ-氨基丁酸。

Conversion of gamma-hydroxybutyrate to gamma-aminobutyrate in vitro.

作者信息

Vayer P, Mandel P, Maitre M

出版信息

J Neurochem. 1985 Sep;45(3):810-4. doi: 10.1111/j.1471-4159.1985.tb04065.x.

DOI:10.1111/j.1471-4159.1985.tb04065.x
PMID:2863327
Abstract

[3H]gamma-Hydroxybutyric acid [( 3H]GHB) at physiological concentration incubated with brain slices in Krebs-Ringer medium produced [3H]gamma-aminobutyric acid [( 3H]GABA). This compound was identified by its Rf values on thin-layer chromatograms and by analysis of the dansyl derivatives of the free amino acid fraction. No labelled glutamate could be detected. Brain slices incubated with labelled glutamate and nonradioactive GHB generated labelled 2-oxoglutarate, suggesting that gamma-aminobutyrate-2-oxoglutarate transaminase (GABA-T) is involved in catalyzing this reaction. Furthermore, specific inhibitors of GABA-T blocked the production of labelled GABA from labelled GHB and of labelled 2-oxoglutarate from labelled glutamate. Transformation of [3H]GHB into [3H]GABA was not inhibited by malonate, demonstrating that the succinate-linked pathway is not involved in the generation of GABA. The kinetic characteristics of the multienzyme system involved in GHB degradation studied in vitro are compatible with the production of GABA in vivo.

摘要

生理浓度的[3H]γ-羟基丁酸([3H]GHB)与置于Krebs-Ringer培养基中的脑片一起孵育时会产生[3H]γ-氨基丁酸([3H]GABA)。该化合物通过其在薄层色谱图上的比移值以及对游离氨基酸部分的丹磺酰衍生物的分析得以鉴定。未检测到标记的谷氨酸。用标记的谷氨酸和非放射性GHB孵育的脑片产生了标记的2-氧代戊二酸,这表明γ-氨基丁酸-2-氧代戊二酸转氨酶(GABA-T)参与催化该反应。此外,GABA-T的特异性抑制剂阻断了由标记的GHB产生标记的GABA以及由标记的谷氨酸产生标记的2-氧代戊二酸的过程。丙二酸不会抑制[3H]GHB向[3H]GABA的转化,这表明琥珀酸连接途径不参与GABA的生成。体外研究的参与GHB降解的多酶系统的动力学特征与体内GABA的产生情况相符。

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1
Conversion of gamma-hydroxybutyrate to gamma-aminobutyrate in vitro.γ-羟基丁酸在体外转化为γ-氨基丁酸。
J Neurochem. 1985 Sep;45(3):810-4. doi: 10.1111/j.1471-4159.1985.tb04065.x.
2
Evidence for a role of high Km aldehyde reductase in the degradation of endogenous gamma-hydroxybutyrate from rat brain.高Km醛还原酶在大鼠脑内源性γ-羟基丁酸降解中作用的证据。
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Studies on the relation of gamma-hydroxybutyric acid (GHB) to gamma-aminobutyric acid (GABA). Evidence that GABA is not the sole source for GHB in rat brain.
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gamma-Hydroxybutyric acid in subcellular fractions of rat brain.大鼠脑亚细胞组分中的γ-羟基丁酸
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In vivo conversion of gamma-aminobutyric acid and 1,4-butanediol to gamma-hydroxybutyric acid in rat brain. Studies using stable isotopes.大鼠脑内γ-氨基丁酸和1,4-丁二醇在体内转化为γ-羟基丁酸。使用稳定同位素的研究。
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gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide.γ-羟基丁酸转化为γ-氨基丁酸会诱导γ-氨基丁酸B型受体结合位点的置换,丙戊酸盐和乙琥胺可阻断这一过程。
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Effects of anticonvulsants on the formation of gamma-hydroxybutyrate from gamma-aminobutyrate in rat brain.
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Endogenous gamma-hydroxybutyrate in rat brain areas: postmortem changes and effects of drugs interfering with gamma-aminobutyric acid metabolism.大鼠脑区中的内源性γ-羟基丁酸:死后变化及干扰γ-氨基丁酸代谢的药物的影响
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Succinic semialdehyde as a substrate for the formation of gamma-aminobutyric acid.琥珀酸半醛作为生成γ-氨基丁酸的底物。
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Glutamate as a precursor of GABA in rat brain and peripheral tissues.谷氨酸作为大鼠脑和外周组织中γ-氨基丁酸的前体。
Mol Cell Biochem. 1981 Sep 25;39:253-9. doi: 10.1007/BF00232578.

引用本文的文献

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γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology.γ-羟基丁酸:药代动力学、药效学和毒理学。
AAPS J. 2021 Jan 8;23(1):22. doi: 10.1208/s12248-020-00543-z.
2
gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness.γ-羟基丁酸/羟丁酸钠:神经生物学及其对睡眠和觉醒的影响
CNS Drugs. 2006;20(12):993-1018. doi: 10.2165/00023210-200620120-00004.
3
gamma-Hydroxybutyric acid (GHBA) induces pacemaker activity and inhibition of substantia nigra dopamine neurons by activating GABAB-receptors.
γ-羟基丁酸(GHBA)通过激活GABAB受体诱导起搏器活动并抑制黑质多巴胺能神经元。
Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):491-7. doi: 10.1007/BF00173208.
4
An overview of gamma-hydroxybutyrate catabolism: the role of the cytosolic NADP(+)-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxoacid transhydrogenase in the initial, rate-limiting step in this pathway.γ-羟基丁酸分解代谢概述:胞质NADP(+)-依赖性氧化还原酶EC 1.1.1.19和线粒体羟酸-氧代酸转氢酶在该途径初始限速步骤中的作用。
Neurochem Res. 1991 Sep;16(9):965-74. doi: 10.1007/BF00965839.