گلوتاتيون

(تم التحويل من Glutathione)
گلوتاتيون[1]
Glutathione-skeletal.svg
Glutathione-from-xtal-3D-balls.png
Glutathione-3D-vdW.png
الأسماء
اسم أيوپاك
γ-Glutamylcysteinylglycine
اسم أيوپاك النظامي
(2S)-2-Amino-5-({(2R)-1-[(carboxymethyl)amino]-1-oxo-3-sulfanylpropan-2-yl}amino)-5-oxopentanoic acid
أسماء أخرى
γ-L-Glutamyl-L-cysteinylglycine
(2S)-2-Amino-4-({(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid
المُعرِّفات
رقم CAS
3D model (JSmol)
اختصارات GSH
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.660 Edit this at Wikidata
KEGG
عناوين مواضيع طبية MeSH {{{value}}}
UNII
الخصائص
الصيغة الجزيئية C10H17N3O6S
كتلة مولية 307.29 g mol-1
نقطة الانصهار
قابلية الذوبان في الماء Freely soluble[1]
قابلية الذوبان في methanol, diethyl ether Insoluble[1]
علم الأدوية
V03AB32 (WHO)
ما لم يُذكر غير ذلك، البيانات المعطاة للمواد في حالاتهم العيارية (عند 25 °س [77 °ف]، 100 kPa).
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مراجع الجدول

الگلوتاتيون Glutathione (GSH)، هو مادة هامة مضادة للأكسدة في النباتات، الحيوانات، الفطريات، وبعض الجراثيم والعتائق، تمنع تضرر المكونات الخلوية بسبب أنواع الأكسجين التفاعلية مثل الجذور الحرة، الپيروكسيدات، پيروكسيدات الدهنية والفلزات الثقيلة.[2] وهو ثلاثي پپتيد برابط گاما پپتيد بين مجموعة كربوكسيل السلسلة الجانبية الگلوتامات ومجموعة السيستئين (والتي ترتبط مع [[برابطة پپتيد عادية مع الگلايسين.

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التخليق الحيوي والتواجد

Glutathione biosynthesis involves two adenosine triphosphate-dependent steps:

While all animal cells are capable of synthesizing glutathione, glutathione synthesis in the liver has been shown to be essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis.[4][5]

The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases.[6]


Occurrence

Glutathione is the most abundant non-protein thiol (R−SH-containing compound) in animal cells, ranging from 0.5 to 10 mmol/L. It is present in the cytosol and the organelles.[6] In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH), with the remainder in the disulfide form (GSSG).[7] 80-85% of cellular GSH is in the cytosol and 10-15% is in the mitochondria.[8]

Human beings synthesize glutathione, but a few eukaryotes do not, including some members of Fabaceae, Entamoeba, and Giardia. The only known archaea that make glutathione are halobacteria. Some bacteria, such as "Cyanobacteria" and Pseudomonadota, can biosynthesize glutathione.[9][10]

Systemic availability of orally consumed glutathione has poor bioavailability because the tripeptide is the substrate of proteases (peptidases) of the alimentary canal, and due to the absence of a specific carrier of glutathione at the level of cell membrane.[11][12] The administration of N-acetylcysteine (NAC), a cysteine prodrug, helps replenish intracellular GSH levels.[13] The patented compound RiboCeine has been studied as a supplement that enhances production of glutathione which helps mitigate hyperglycemia.[14][15]

الوظيفة الكيميائية الحيوية

Glutathione exists in reduced (GSH) and oxidized (GSSG) states.[16] The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress[17][8] where increased GSSG-to-GSH ratio is indicative of greater oxidative stress.

In the reduced state, the thiol group of cysteinyl residue is a source of one reducing equivalent. Glutathione disulfide (GSSG) is thereby generated. The oxidized state is converted to the reduced state by NADPH.[18] This conversion is catalyzed by glutathione reductase:

NADPH + GSSG + H2O → 2 GSH + NADP+ + OH−

الأدوار

Antioxidant

GSH protects cells by neutralising (reducing) reactive oxygen species.[19][6] This conversion is illustrated by the reduction of peroxides:

2 GSH + R2O2 → GSSG + 2 ROH  (R = H, alkyl)

and with free radicals:

GSH + R• → 1/2 GSSG + RH

Regulation

Aside from deactivating radicals and reactive oxidants, glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein S-glutathionylation, a redox-regulated post-translational thiol modification. The general reaction involves formation of an unsymmetrical disulfide from the protectable protein (RSH) and GSH:[20]

RSH + GSH + [O] → GSSR + H2O

Glutathione is also employed for the detoxification of methylglyoxal and formaldehyde, toxic metabolites produced under oxidative stress. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoylglutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-lactoylglutathione to glutathione and D-lactic acid.

It maintains exogenous antioxidants such as vitamins C and E in their reduced (active) states.[21][22][23]

Metabolism

Among the many metabolic processes in which it participates, glutathione is required for the biosynthesis of leukotrienes and prostaglandins. It plays a role in the storage of cysteine. Glutathione enhances the function of citrulline as part of the nitric oxide cycle.[24] It is a cofactor and acts on glutathione peroxidase.[25] Glutathione is used to produce S-sulfanylglutathione, which is part of hydrogen sulfide metabolism.[26]

Conjugation

Glutathione facilitates metabolism of xenobiotics. Glutathione S-transferase enzymes catalyze its conjugation to lipophilic xenobiotics, facilitating their excretion or further metabolism.[27] The conjugation process is illustrated by the metabolism of N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is a reactive metabolite formed by the action of cytochrome P450 on paracetamol (acetaminophen). Glutathione conjugates to NAPQI, and the resulting ensemble is excreted.

في النبات

In plants, glutathione is involved in stress management. It is a component of the glutathione-ascorbate cycle, a system that reduces poisonous hydrogen peroxide.[28] It is the precursor of phytochelatins, glutathione oligomers that chelate heavy metals such as cadmium.[29] Glutathione is required for efficient defence against plant pathogens such as Pseudomonas syringae and Phytophthora brassicae.[30] Adenylyl-sulfate reductase, an enzyme of the sulfur assimilation pathway, uses glutathione as an electron donor. Other enzymes using glutathione as a substrate are glutaredoxins. These small oxidoreductases are involved in flower development, salicylic acid, and plant defence signalling.[31]

الاستخدامات

صناعة النبيذ

The content of glutathione in must, the first raw form of wine, determines the browning, or caramelizing effect, during the production of white wine by trapping the caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product.[32] Its concentration in wine can be determined by UPLC-MRM mass spectrometry.[33]

انظر أيضاً


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المصادر

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