麩胱甘肽
麩胱甘肽 | |
---|---|
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 |
莫耳質量 | 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,所有資料均出自標準狀態(25 ℃,100 kPa)下。 |
麩胱甘肽(英語:Glutathione,簡稱:GSH),又稱穀胱甘肽或麩胺基硫,[1]屬於三肽,由麩胺酸、半胱胺酸及甘胺酸所構成,其中第一個肽鍵與普通的肽鍵不同,是由麩胺酸的γ-羧基與半胱胺酸的胺基組成的,在分子中半胱胺酸巰基是該化合物的主要功能基團。麩胱甘肽是植物、動物、真菌和一些細菌和古菌中的一種抗氧化劑。麩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。麩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。菠菜含有麩胱甘肽。
生物合成和儲存
[編輯]麩胱甘肽生物合成涉及兩個三磷酸腺苷依賴的步驟:
- 首先,γ-麩胺醯半胱胺酸由 L-麩胺酸和 L-半胱胺酸合成。此轉化需要酶麩胺酸-半胱胺酸連接酶 (GCL,麩胺酸半胱胺酸合酶)。此反應是麩胱甘肽合成中的限速步驟。[3]
- 其次,將甘胺酸添加到γ-麩胺醯半胱胺酸的C末端。該縮合反應由麩胱甘肽合成酶催化。
雖然所有動物細胞都能夠合成麩胱甘肽,但已證明肝臟中的麩胱甘肽合成至關重要。GCLC基因剔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] 麩胱甘肽中不尋常的γ醯胺鍵保護它免受肽酶的水解。[6]
儲存
[編輯]麩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。它存在於細胞質和胞器中。在健康細胞和組織中,[6]總麩胱甘肽池的 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% 存在於粒線體中。[8]
人體能夠合成麩胱甘肽,但少數真核生物不會合成麩胱甘肽,包括豆科植物、內阿米巴屬和賈第鞭毛蟲屬的部分成員。已知唯一能合成麩胱甘肽的古細菌是鹽桿菌綱。某些細菌,如「藍藻」和假單胞菌,可以生物合成麩胱甘肽。[9][10]
口服麩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)的受質,並且由於細胞膜水平上缺乏麩胱甘肽的特定載體。[11][12]服用半胱胺酸前體藥物 N-乙醯半胱胺酸 (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,可增強麩胱甘肽的產生,從而有助於緩解高血糖。[14][15]
生物學功能
[編輯]麩胱甘肽以還原(GSH)和氧化(GSSG)狀態存在。[16]細胞內還原麩胱甘肽與氧化麩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。由此生成麩胱甘肽二硫化物 (GSSG)的氧化狀態通過NADPH[18]轉化為還原狀態(GSH)。該轉化由麩胱甘肽還原酶催化
- 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,麩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」-麩胱甘肽化,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
麩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麩胱甘肽轉化為 S-D-乳醯麩胱甘肽。乙二醛酶II (EC 3.1.2.6) 催化 S-D-乳醯麩胱甘肽水解為麩胱甘肽和D-乳酸。
它維持外源性抗氧化劑如維生素C和維生素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,麩胱甘肽是白三烯和前列腺素生物合成所必需的。它在半胱胺酸的儲存中發揮作用。麩胱甘肽增強了瓜胺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麩胱甘肽過氧化物酶。[25] 麩胱甘肽用於生成 S-硫烷基麩胱甘肽,它是硫化氫代謝的一部分。[26]
結合
[編輯]麩胱甘肽促進外來化合物代謝。麩胱甘肽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-乙醯基-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作用於對乙醯胺基酚(乙醯胺基酚) 而形成。麩胱甘肽與 NAPQI 結合,並將所得複合物排出體外。
在植物中
[編輯]在植物中,麩胱甘肽參與活性氧壓力管理。它是麩胱甘肽-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、麩胱甘肽低聚物的前體,可以螯合鎘等重金屬。[29]麩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,它使用麩胱甘肽作為電子供體。其他使用麩胱甘肽作為受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麩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醯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
[編輯]- ^ 1.0 1.1 1.2 1.3 Haynes, William M. (編). CRC Handbook of Chemistry and Physics 97th. CRC Press. 2016: 3.284. ISBN 9781498754293.
- ^ Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF. The changing faces of glutathione, a cellular protagonist. Biochemical Pharmacology. October 2003, 66 (8): 1499–1503. PMID 14555227. doi:10.1016/S0006-2952(03)00504-5.
- ^ White CC, Viernes H, Krejsa CM, Botta D, Kavanagh TJ. Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity. Analytical Biochemistry. July 2003, 318 (2): 175–180 [2024-03-22]. PMID 12814619. doi:10.1016/S0003-2697(03)00143-X. (原始內容存檔於2020-09-27).
- ^ Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP. Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. Hepatology. May 2007, 45 (5): 1118–1128. PMID 17464988. S2CID 25000753. doi:10.1002/hep.21635 .
- ^ Sies H. Glutathione and its role in cellular functions. Free Radical Biology & Medicine. 1999, 27 (9–10): 916–921. PMID 10569624. doi:10.1016/S0891-5849(99)00177-X.
- ^ 6.0 6.1 6.2 Guoyao Wu; Yun-Zhong Fang; Sheng Yang; Joanne R. Lupton; Nancy D. Turner. Glutathione Metabolism and its Implications for Health. Journal of Nutrition. 2004, 134 (3): 489–492. PMID 14988435. doi:10.1093/jn/134.3.489 .
- ^ Halprin KM, Ohkawara A. The measurement of glutathione in human epidermis using glutathione reductase. The Journal of Investigative Dermatology. 1967, 48 (2): 149–152. PMID 6020678. doi:10.1038/jid.1967.24 .
- ^ 8.0 8.1 Lu SC. Glutathione synthesis. Biochimica et Biophysica Acta. May 2013, 1830 (5): 3143–3153. PMC 3549305 . PMID 22995213. doi:10.1016/j.bbagen.2012.09.008.
- ^ Copley SD, Dhillon JK. Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes. Genome Biology. 29 April 2002, 3 (5): research0025. PMC 115227 . PMID 12049666. doi:10.1186/gb-2002-3-5-research0025 .
- ^ Wonisch W, Schaur RJ. Chapter 2: Chemistry of Glutathione. Grill D, Tausz T, De Kok LJ (編). Significance of glutathione in plant adaptation to the environment. Springer. 2001. ISBN 978-1-4020-0178-9 –透過Google Books.
- ^ Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. European Journal of Clinical Pharmacology. 1992, 43 (6): 667–669. PMID 1362956. S2CID 27606314. doi:10.1007/bf02284971.
- ^ Acetylcysteine Monograph for Professionals. Drugs.com. [2024-03-23]. (原始內容存檔於2015-09-23).
- ^ Atkuri, K. R.; Mantovani, J. J.; Herzenberg, L. A.; Herzenberg, L. A. N-acetylcysteine - a safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology. 2007, 7 (4): 355–359. PMC 4540061 . PMID 17602868. doi:10.1016/j.coph.2007.04.005.
- ^ Nagasawa, Herbert T. COMPOSITIONS COMPRISING SUGAR-CYSTEINE PRODUCTS - US-20140348811-A1. ppubs.uspto.gov. United States Patent Office: 16. November 27, 2014 [October 31, 2023]. (原始內容存檔於2023-10-31).
30. A method of increasing ATP and/or glutathione...
- ^ Ukwenya VO, Alese MO, Ogunlade B, Folorunso IM, Omotuyi OI. Anacardium occidentale leaves extract and riboceine mitigate hyperglycemia through anti-oxidative effects and modulation of some selected genes associated with diabetes. J Diabetes Metab Disord. 2022, 22 (1): 455–468. PMC 10225389 . PMID 37255827. doi:10.1007/s40200-022-01165-2.
- ^ Iskusnykh IY, Zakharova AA, Pathak D. Glutathione in Brain Disorders and Aging. Molecules. January 2022, 27 (1): 324. PMC 8746815 . PMID 35011559. doi:10.3390/molecules27010324 .
- ^ Pastore A, Piemonte F, Locatelli M, Lo Russo A, Gaeta LM, Tozzi G, Federici G. Determination of blood total, reduced, and oxidized glutathione in pediatric subjects. Clinical Chemistry. August 2001, 47 (8): 1467–1469 [2024-03-21]. PMID 11468240. doi:10.1093/clinchem/47.8.1467 . (原始內容存檔於2016-03-03).
- ^ Couto N, Malys N, Gaskell SJ, Barber J. Partition and turnover of glutathione reductase from Saccharomyces cerevisiae: a proteomic approach (PDF). Journal of Proteome Research. June 2013, 12 (6): 2885–2894 [2024-03-21]. PMID 23631642. doi:10.1021/pr4001948. (原始內容存檔 (PDF)於2024-03-19).
- ^ Michael Brownlee. The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 2005, 54 (6): 1615–1625. PMID 15919781. doi:10.2337/diabetes.54.6.1615 .
- ^ Dalle-Donne, Isabella; Rossi, Ranieri; Colombo, Graziano; Giustarini, Daniela; Milzani, Aldo. Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends in Biochemical Sciences. 2009, 34 (2): 85–96. PMID 19135374. doi:10.1016/j.tibs.2008.11.002.
- ^ Dringen R. Metabolism and functions of glutathione in brain. Progress in Neurobiology. December 2000, 62 (6): 649–671. PMID 10880854. S2CID 452394. doi:10.1016/s0301-0082(99)00060-x.
- ^ Scholz RW, Graham KS, Gumpricht E, Reddy CC. Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation. Annals of the New York Academy of Sciences. 1989, 570 (1): 514–517. Bibcode:1989NYASA.570..514S. S2CID 85414084. doi:10.1111/j.1749-6632.1989.tb14973.x.
- ^ Hughes RE. Reduction of dehydroascorbic acid by animal tissues. Nature. 1964, 203 (4949): 1068–1069. Bibcode:1964Natur.203.1068H. PMID 14223080. S2CID 4273230. doi:10.1038/2031068a0.
- ^ Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS. Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe. The Plant Cell. June 1999, 11 (6): 1153–1164. JSTOR 3870806. PMC 144235 . PMID 10368185. doi:10.1105/tpc.11.6.1153.
- ^ Grant CM. Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Molecular Microbiology. 2001, 39 (3): 533–541. PMID 11169096. S2CID 6467802. doi:10.1046/j.1365-2958.2001.02283.x .
- ^ Melideo, SL; Jackson, MR; Jorns, MS. Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog.. Biochemistry. 22 July 2014, 53 (28): 4739–53. PMC 4108183 . PMID 24981631. doi:10.1021/bi500650h.
- ^ Hayes, John D.; Flanagan, Jack U.; Jowsey, Ian R. Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005, 45: 51–88. PMID 15822171. doi:10.1146/annurev.pharmtox.45.120403.095857.
- ^ Noctor G, Foyer CH. Ascorbate and Glutathione: Keeping Active Oxygen Under Control. Annual Review of Plant Physiology and Plant Molecular Biology. June 1998, 49 (1): 249–279. PMID 15012235. doi:10.1146/annurev.arplant.49.1.249.
- ^ Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS. Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe. The Plant Cell. June 1999, 11 (6): 1153–1164. PMC 144235 . PMID 10368185. doi:10.1105/tpc.11.6.1153.
- ^ Parisy V, Poinssot B, Owsianowski L, Buchala A, Glazebrook J, Mauch F. Identification of PAD2 as a gamma-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis (PDF). The Plant Journal. January 2007, 49 (1): 159–172 [2024-04-04]. PMID 17144898. doi:10.1111/j.1365-313X.2006.02938.x . (原始內容存檔 (PDF)於2022-04-03).
- ^ Rouhier N, Lemaire SD, Jacquot JP. The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation (PDF). Annual Review of Plant Biology. 2008, 59 (1): 143–166 [2024-04-04]. PMID 18444899. doi:10.1146/annurev.arplant.59.032607.092811. (原始內容存檔 (PDF)於2024-01-07).
- ^ Rigaud J, Cheynier V, Souquet JM, Moutounet M. Influence of must composition on phenolic oxidation kinetics. Journal of the Science of Food and Agriculture. 1991, 57 (1): 55–63. Bibcode:1991JSFA...57...55R. doi:10.1002/jsfa.2740570107.
- ^ Vallverdú-Queralt A, Verbaere A, Meudec E, Cheynier V, Sommerer N. Straightforward method to quantify GSH, GSSG, GRP, and hydroxycinnamic acids in wines by UPLC-MRM-MS. Journal of Agricultural and Food Chemistry. January 2015, 63 (1): 142–149. PMID 25457918. doi:10.1021/jf504383g.