穀胱甘肽
穀胱甘肽 | |
---|---|
IUPAC名 γ-Glutamylcysteinylglycine | |
別名 | γ-L-Glutamyl-L-cysteinylglycine (2S)-2-Amino-4-({(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid |
縮寫 | GSH |
識別 | |
CAS號 | 70-18-8 |
PubChem | 124886 |
ChemSpider | 111188 |
SMILES |
|
ChEBI | 16856 |
DrugBank | DB00143 |
KEGG | C00051 |
MeSH | Glutathione |
性質 | |
化學式 | C10H17N3O6S |
摩爾質量 | 307.325 g·mol⁻¹ |
熔點 | 195[1] |
溶解性(水) | 易溶[1] |
溶解性(甲醇, 乙醚) | 不溶[1] |
藥理學 | |
ATC代碼 | V03AB32(V03) |
若非註明,所有數據均出自標準狀態(25 ℃,100 kPa)下。 |
穀胱甘肽(英語:Glutathione,簡稱:GSH),又稱麩胱甘肽或麩氨基硫,[1]屬於三肽,由穀氨酸、半胱氨酸及甘氨酸所構成,其中第一個肽鍵與普通的肽鍵不同,是由穀氨酸的γ-羧基與半胱氨酸的氨基組成的,在分子中半胱氨酸巰基是該化合物的主要功能基團。穀胱甘肽是植物、動物、真菌和一些細菌和古菌中的一種抗氧化劑。穀胱甘肽能夠防止活性氧、自由基、過氧化物、脂質過氧化物和重金屬等來源對重要細胞成分造成的損害。[2] 作為動物細胞中的抗氧化劑,存在於充滿水的細胞內部,可以保護DNA免於氧化。穀胱甘肽以兩種型態存在於人體,一是還原型態、另一是氧化型態。菠菜含有穀胱甘肽。
生物合成和儲存
[編輯]穀胱甘肽生物合成涉及兩個三磷酸腺苷依賴的步驟:
- 首先,γ-麩胺醯半胱氨酸由 L-穀氨酸和 L-半胱氨酸合成。此轉化需要酶穀氨酸-半胱氨酸連接酶 (GCL,穀氨酸半胱氨酸合酶)。此反應是穀胱甘肽合成中的限速步驟。[3]
- 其次,將甘氨酸添加到γ-麩胺醯半胱氨酸的C末端。該縮合反應由穀胱甘肽合成酶催化。
雖然所有動物細胞都能夠合成穀胱甘肽,但已證明肝臟中的穀胱甘肽合成至關重要。GCLC基因敲除小鼠由於缺乏肝臟GSH合成而在出生後一個月內死亡。[4][5] 穀胱甘肽中不尋常的γ酰胺鍵保護它免受肽酶的水解。[6]
儲存
[編輯]穀胱甘肽是動物細胞中最豐富的非蛋白硫醇(含 R-SH 的化合物),含量範圍為 0.5 至 10 mmol/L。它存在於細胞質和細胞器中。在健康細胞和組織中,[6]總穀胱甘肽池的 90% 以上為還原形式(GSH),其餘為二硫化物氧化形式(GSSG)。[7]80-85% 的細胞GSH存在於細胞質中,10-15% 存在於線粒體中。[8]
人體能夠合成穀胱甘肽,但少數真核生物不會合成穀胱甘肽,包括豆科植物、內阿米巴屬和賈第鞭毛蟲屬的部分成員。已知唯一能合成穀胱甘肽的古細菌是鹽桿菌綱。某些細菌,如「藍藻」和假單胞菌,可以生物合成穀胱甘肽。[9][10]
口服穀胱甘肽的全身利用度生物利用度較差,因為三肽是消化道蛋白酶(肽酶)的基質,並且由於細胞膜水平上缺乏穀胱甘肽的特定載體。[11][12]服用半胱氨酸前體藥物 N-乙酰半胱氨酸 (NAC) 有助於補充細胞內 GSH 水平。[13]專利化合物 RiboCeine 已被研究作為一種補充劑,可增強穀胱甘肽的產生,從而有助於緩解高血糖。[14][15]
生物學功能
[編輯]穀胱甘肽以還原(GSH)和氧化(GSSG)狀態存在。[16]細胞內還原穀胱甘肽與氧化穀胱甘肽的比率是細胞氧化應激的量度,[17][8]其中 GSSG 與 GSH 比率增加表明氧化應激更大。
在還原狀態下,半胱胺醯殘基的硫醇基團是一個還原當量的來源。由此生成穀胱甘肽二硫化物 (GSSG)的氧化狀態通過NADPH[18]轉化為還原狀態(GSH)。該轉化由穀胱甘肽還原酶催化
- NADPH + GSSG + H2O → 2 GSH + NADP+ + OH−
作用
[編輯]抗氧化劑
[編輯]GSH通過中和(減少)活性氧來保護細胞。[19][6]這種轉化可以通過過氧化物的還原來說明:
- 2 GSH + R2O2 → GSSG + 2 ROH (R = 氫,烷基 )
以及自由基:
- GSH + R• → 1/2 GSSG + RH
調節
[編輯]除了使自由基和活性氧化劑失活外,穀胱甘肽還參與硫醇保護和氧化應激下細胞硫醇蛋白的氧化還原調節,通過蛋白質「S」-穀胱甘肽化,一種氧化還原調節的轉譯後硫醇修飾。一般反應涉及從可保護蛋白質 (RSH) 和 GSH 形成不對稱二硫化物:[20]
- RSH + GSH + [O] → GSSR + H2O
穀胱甘肽還用於解毒氧化應激產生的有毒代謝物甲基乙二醛和甲醛。該解毒反應由乙二醛酶系統進行。乙二醛酶I (EC 4.4.1.5) 催化甲基乙二醛和還原穀胱甘肽轉化為 S-D-乳酰穀胱甘肽。乙二醛酶II (EC 3.1.2.6) 催化 S-D-乳酰穀胱甘肽水解為穀胱甘肽和D-乳酸。
它維持外源性抗氧化劑如維他命C和維他命E處於還原(活性)狀態。[21][22][23]
新陳代謝
[編輯]在其參與的眾多代謝過程中,穀胱甘肽是白三烯和前列腺素生物合成所必需的。它在半胱氨酸的儲存中發揮作用。穀胱甘肽增強了瓜氨酸作為一氧化氮循環一部分的功能。[24]它是一種輔因子並作用於穀胱甘肽過氧化物酶。[25] 穀胱甘肽用於生成 S-硫烷基穀胱甘肽,它是硫化氫代謝的一部分。[26]
結合
[編輯]穀胱甘肽促進外來化合物代謝。穀胱甘肽S-轉移酶催化其與親脂性外來化合物結合,促進其排泄或進一步代謝。[27]結合過程以N-乙酰基-p-苯醌亞胺(NAPQI) 的代謝為例。NAPQI 是一種活性代謝物,由細胞色素 P450作用於對乙酰氨基酚(乙酰氨基酚) 而形成。穀胱甘肽與 NAPQI 結合,並將所得複合物排出體外。
在植物中
[編輯]在植物中,穀胱甘肽參與活性氧壓力管理。它是穀胱甘肽-抗壞血酸循環的組成部分,該系統可減少有毒的過氧化氫。[28] 它是植物螯合素、穀胱甘肽低聚物的前體,可以螯合鎘等重金屬。[29]穀胱甘肽是有效防禦植物病原體(例如「丁香假單胞菌」和「芸苔疫黴菌」)所必需的。[30]腺苷酸硫酸還原酶是硫同化途徑的一種酶,它使用穀胱甘肽作為電子供體。其他使用穀胱甘肽作為基質的酶是谷氧還蛋白。這些小的氧化還原酶參與了花的發育、水楊酸和植物防禦信號傳導。[31]
用途
[編輯]釀酒
[編輯]葡萄酒的第一個原料形式葡萄漿中的穀胱甘肽含量決定了白葡萄酒生產過程中的褐變或焦糖化效果,因為它可以捕獲酶氧化產生的咖啡酰酒石酸醌作為葡萄反應產物。[32]可以通過UPLC-MRM質譜法測定葡萄酒中的該物質的濃度。[33]
參考文獻
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