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2025年11月3日 星期一

Glutathione conjugation

Glutathione conjugation

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2025-11-04
Glutathione conjugation - PATHWAY SUMMARY

Source or References (
資訊來源或是參考的資訊):
https://pubchem.ncbi.nlm.nih.gov/pathway/Reactome:R-HSA-156590
Info cited on 2025-11-04-WD2 (
資訊引用於 中華民國114年西元2025114) by 湯偉晉 (WeiJin Tang)
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Glutathione conjugation - PATHWAY SUMMARY

Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes. They can be found in the cytosol as well as being microsomal membrane-bound. Cytosolic GSTs are encoded by at least 5 gene families (alpha, mu, pi, theta and zeta GST) whereas membrane-bound enzymes are encoded by single genes. Soluble GSTs are homo- or hetero-dimeric enzymes (approximately 25KDa subunits) which can act on a wide range of endogenous and exogenous electrophiles. GSTs mediate conjugation using glutathione (GSH), a tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine. A generalized reaction is RX + GSH -> HX + GSR Glutathione conjugates are excreted in bile and converted to cysteine and mercapturic acid conjugates in the intestine and kidneys. GSH is the major, low molecular weight, non-protein thiol synthesized de novo in mammalian cells. As well as taking part in conjugation reactions, GSH also has antioxidant ability and can metabolize endogenous and exogenous compounds. The nucleophilic GSH attacks the electrophilic substrate forming a thioether bond between the cysteine residue of GSH and the electrophile. The result is generally a less reactive and more water-soluble conjugate that can be easily excreted. In some cases, GSTs can activate compounds to reactive species such as certain haloalkanes and haloalkenes. Substrates for GSTs include epoxides, alkenes and compounds with electrophilic carbon, sulfur or nitrogen centres. There are two types of conjugation reaction with glutathione: displacement reactions where glutathione displaces an electron-withdrawing group and addition reactions where glutathione is added to activated double bond structures or strained ring systems.
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好的,WeiJin(偉晉),以下是這段關於 Glutathione S-Transferases (GSTs) 的英文與繁體中文逐句對照翻譯。
我保留了原文的專業詞彙與生化名詞,以符合學術用途。

Glutathione transferases
穀胱甘肽轉移酶
Glutathione transferases (
穀胱甘肽轉移酶)
穀胱甘肽轉移酶 (Glutathione transferases)

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Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes.
穀胱甘肽轉移酶(Glutathione S-Transferases, GSTsEC 2.5.1.18 是另一大類屬於第二相(Phase II)結合反應酶系的重要酵素群。

They can be found in the cytosol as well as being microsomal membrane-bound.
它們既存在於 細胞質液(cytosol中,也以膜結合型形式附著在微粒體microsomes)膜上。

microsome (
微粒體)

gene families
基因家族
gene families (
基因家族)
基因家族 (gene families)

Cytosolic GSTs
細胞質型的GSTs
Cytosolic GSTs (
細胞質型的GSTs)
細胞質型的GSTs (Cytosolic GSTs)

Cytosolic GSTs are encoded by at least 5 gene families (alpha, mu, pi, theta and zeta GST) whereas membrane-bound enzymes are encoded by single genes.
細胞質型的GSTs 由至少 五個基因家族 編碼,分別為 α(alpha)、μ(mu)、π(pi)、θ(theta ζ(zeta 類;
而膜結合型酵素則由單一基因所編碼。

Soluble GSTs are homo- or hetero-dimeric enzymes (approximately 25KDa subunits) which can act on a wide range of endogenous and exogenous electrophiles.
可溶性GSTs 為同源或異源二聚體酵素(每個亞基約25 kDa),能夠作用於多種內源性與外源性 親電子化合物(electrophiles)。

electrophile
親電子化合物
electrophile (
親電子化合物)
親電子化合物 (electrophile)

electrophiles
親電子化合物
electrophiles (
親電子化合物)
親電子化合物 (electrophiles)

GSTs mediate conjugation using glutathione (GSH), a tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine.
GSTs
以穀胱甘肽(GSH)作為輔基進行結合反應
GSH
是由其前驅胺基酸 γ-谷氨酸(gamma-glutamate)、半胱胺酸(cysteine 甘胺酸(glycine 組成的三胜肽。

precursor amino acid
前驅胺基酸
precursor amino acid (
前驅胺基酸)
前驅胺基酸 (precursor amino acid)

precursor amino acids
前驅胺基酸
precursor amino acids (
前驅胺基酸)
前驅胺基酸 (precursor amino acids)

A generalized reaction is RX + GSH
HX + GSR.
一般反應式為:RX + GSH HX + GSR

Glutathione conjugates are excreted in bile and converted to cysteine and mercapturic acid conjugates in the intestine and kidneys.
穀胱甘肽結合物(GSH conjugates 通常經由膽汁排泄,並在腸道與腎臟中被轉化為半胱胺酸結合物與巰基尿酸(mercapturic acid)結合物。

GSH is the major, low molecular weight, non-protein thiol synthesized de novo in mammalian cells.
GSH
是哺乳動物細胞中主要的、低分子量的、非蛋白質型巰基化合物(thiol),可經由體內新生合成(de novo synthesis)獲得。

As well as taking part in conjugation reactions, GSH also has antioxidant ability and can metabolize endogenous and exogenous compounds.
除了參與結合反應外,GSH 還具有抗氧化能力(antioxidant ability),能代謝多種內源性與外源性化合物。

The nucleophilic GSH attacks the electrophilic substrate forming a thioether bond between the cysteine residue of GSH and the electrophile.
具親核性的GSH 攻擊親電子性底物,在 GSH 的半胱胺酸殘基與親電子物之間形成硫醚鍵(thioether bond)。

nucleophilic
親核性的
nucleophilic (
親核性的)
親核性的 (nucleophilic)

thioether bond
硫醚鍵
thioether bond (
硫醚鍵)
硫醚鍵 (thioether bond)

The result is generally a less reactive and more water-soluble conjugate that can be easily excreted.
其結果通常產生反應性較低、親水性較高的結合物,能被容易排出體外。

In some cases, GSTs can activate compounds to reactive species such as certain haloalkanes and haloalkenes.
在某些情況下,GSTs 甚至能將化合物活化為具有反應性的中間物種,例如某些鹵代烷(haloalkanes)與鹵代烯(haloalkenes)。

Substrates for GSTs include epoxides, alkenes and compounds with electrophilic carbon, sulfur or nitrogen centres.
GSTs
的底物包括環氧化物(epoxides)、烯類化合物(alkenes)以及含有親電子性碳、硫或氮中心的化合物。

There are two types of conjugation reaction with glutathione: displacement reactions where glutathione displaces an electron-withdrawing group and addition reactions where glutathione is added to activated double bond structures or strained ring systems.
與穀胱甘肽相關的結合反應主要分為兩種類型:
1)取代反應(displacement reactions)——GSH 取代親電子基團中的吸電子基(electron-withdrawing group);
2)加成反應(addition reactions)——GSH 加成至活化的雙鍵結構或張力環系統(strained ring systems)上。

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資訊來源:
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