Question 1

What is Glutathione?

Accepted Answer

"Glutathione, a major cellular non-protein thiol (NPSH), serves a central role in repairing damage induced by cancer drugs, pollutants and radiation and in the detoxification of several cancer chemotherapeutic drugs and toxins." Quote source / Credit:  https://pubmed.ncbi.nlm.nih.gov/24149024/

"It is hard to overstate the importance of glutathione, key roles of which are summarized (below).  It plays a crucial role in shielding cellular macromolecules from endogenous and exogenous reactive oxygen and nitrogen species. While it directly quenches some free radicals, of perhaps greater importance is that it deals directly with the causes of oxidative stress such as mercury and POPs."

"The Critical Roles of Glutathione:
Direct chemical neutralization of singlet oxygen, hydroxyl radicals, and superoxide radicals
Cofactor for several antioxidant enzymes
Regeneration of vitamins C and E
Neutralization of free radicals produced by Phase I liver metabolism of chemical toxins
One of approximately 7 liver Phase II reactions, which conjugate the activated intermediates produced by Phase I to make them water soluble for excretion by the kidneys
Transportation of mercury out of cells and the brain
Regulation of cellular proliferation and apoptosis
Vital to mitochondrial function and maintenance of mitochondrial DNA (mtDNA)"

"Glutathione is involved in the detoxification of both xenobiotic and endogenous compounds. It facilitates excretion from cells (Hg), facilitates excretion from body (POPs, Hg) and directly neutralizes (POPs, many oxidative chemicals). Glutathione facilitates the plasma membrane transport of toxins by at least 4 different mechanisms, the most important of which is formation of glutathione S-conjugates. Low levels of glutathione and/or transferase activity are also associated with chronic exposure to chemical toxins and alcohol, cadmium exposure, AIDS/HIV, macular degeneration, Parkinson’s disease, and other neurodegenerative disorders.
Glutathione directly scavenges diverse oxidants: superoxide anion, hydroxyl radical, nitric oxide, and carbon radicals. Glutathione catalytically detoxifies: hydroperoxides, peroxynitrites, and lipid peroxides... Another way glutathione protects cells from oxidants is through recycling of vitamins C and E..."
Quotes Source / Credit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/

Question 2

What is Oxidative Stress and Reactive Oxygen Species (ROS)?

Accepted Answer

"Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies." Quote source / credit: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055301/#:~:text=Oxidative%20stress%20refers%20to%20elevated,to%20a%20myriad%20of%20pathologies.

"Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress)." Quote source / credit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/

Question 3

How is Glutathione recycling measured?

Accepted Answer

"We have recently demonstrated in a series of publications that GSH recycling (GSH → GSSG (oxidized GSH) → GSH), which is dependent on several GSH dependent pathways, is required for the metabolic conversion of hydroxyethyldisulfide (HEDS) into mercaptoethanol (ME) (Ayene, Biaglow, Kachur, Stamato, & Koch, 2008; Ayene, et al., 2000; Ayene, et al., 2002; Biaglow, et al., 2003; Biaglow, et al., 2000; Biaglow,et al., 2006; Biaglow, et al., 1998; Li, Ayene, Ward, Dayanandam, & Ayene, 2009; Li, et al., 2013; Li,Zhang, Ward, Prendergast, & Ayene, 2012; Tuttle, et al., 2007)."

"Unlike all the previous assays that measured just the glutathione level, a functional assay for glutathione such as HEDS metabolism will measure the “GSH dependent antioxidant capacity” of cells, a process that requires “glutathione recycling” by oxidative pentose phosphate cycle (OPPC) in conjunction with other GSH dependent pathways (Ayene, et al., 2002; Biaglow, et al., 2003; Lushchak, 2012). Defect in GSH recycling due to damage to cytosolic pathways, oxidative stress, decreased GSH synthesis and/or loss of GSH by other mechanisms in cells is expected to affect the conversion of HEDS into ME (Ayene, et al., 2008; Ayene, et al., 2002; Biaglow, et al., 2003; Lushchak, 2012; Raza & John, 2012)."

"This type of assay would be more appropriate in determining an individual’s antioxidant capacity and the efficacy of dietary supplements, new drugs and antioxidants since it can be used to identify those supplements that improve the overall glutathione-dependent antioxidant capacity of cells before and after an oxidative/toxic insult. Although we have demonstrated HEDS to ME bioconversion in cell culture using HPLC/EC detection and Ellman’s reagent, it is not clear whether a reliable HEDS based test could be developed to quantify glutathione function i.e. glutathione-dependent antioxidant capacity in whole blood and cells and its application in measuring environmental pollutantsinduced damage to GSH dependent antioxidant capacity (Ayene, et al., 2008; Ayene, et al., 2002; Biaglow, et al., 2003; Biaglow, et al., 2006; Lushchak, 2012; Raza & John, 2012)."

Quotes source / credit: https://pubmed.ncbi.nlm.nih.gov/24149024/

Home > Facts & Studies > Recycling Facts

Glutathione Recycling Facts

What is Glutathione?

What is Oxidative Stress and Reactive Oxygen Species (ROS)?

How is Glutathione recycling measured?

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