What is Glutathione?

Definition of Glutathione

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine) is a tripeptide composed of L-glutamic acid, L-cysteine, and glycine. It is a bioactive non-protein mercaptan compound that is widely found in living organisms. In animal and plant cells, Glutathione mainly exists in two forms: reduced glutathione (GSH) and oxidized glutathione (GSSG), of which active GSH accounts for about 90%. GSSG can be reduced to GSH by Glutathione Reductase (GR). And it consumes NADPH. In addition to GSSG, GSH can also form other mixed disulfide mercaptan compounds such as GS-COA, GS-CYS, etc. The chemical structure of glutathione determines its structural stability. Its glycine residues protect glutathione from gamma-glutamyl Cyclotransferase (gamma-GCT). The gamma-peptide bond between glutamate and cysteine prevents glutathione from being hydrolyzed by many polypeptidases.

Natural Sources of Glutathione

While glutathione is primarily synthesized within cells, its levels can be influenced by dietary intake of its precursor amino acids—cysteine, glutamine, and glycine. Foods rich in sulfur-containing amino acids, such as whey protein, cruciferous vegetables (e.g., broccoli, Brussels sprouts), and certain meats, can support glutathione synthesis indirectly by providing substrates needed for its production.

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Glutathione Metabolism

Metabolism of glutathione in animals and plants is accomplished through the gamma-glutamyl cycle. The sulfhydryl group in GSH molecule is the main functional group, which has reducibility and is an important antioxidant in the body. First of all, under the catalysis of glutathione peroxidase, GSH can reduce the H2O2 produced in the cell, making it become H2O, and can remove H2O2 and other peroxides (ROOH), as shown in the following figure. At the same time, GSH is oxidized to oxidized glutathione (GSSG). The latter is catalyzed by glutathione reductase and generated by 2H reduction provided by NADPH & H+ for recycling.

Schematic diagram of the gamma-glutamyl cycle.Overview of gamma-glutamyl cycle. (Paul, N.B.; et al, 2022)

What is Liposomal Glutathione?

Liposomal glutathione refers to a formulation where glutathione is encapsulated within liposomes—small lipid vesicles. This delivery method enhances glutathione's bioavailability and absorption, allowing for better uptake by cells compared to traditional oral supplements. Liposomal encapsulation protects glutathione from degradation in the digestive tract, facilitating its delivery into systemic circulation and intracellular spaces where it exerts its antioxidant effects.

Benefits of Glutathione

GSH is an important antioxidant in the body, protecting the sulfhydryl group in the protein or enzyme molecules in the body from oxidation, so that the protein or enzyme is in an active state, which is reflected in the following aspects:

  • For red blood cells, GSH plays an extremely important role in protecting the integrity of the red blood cell membrane. For example, in people with deficiency of glucose 6-phosphate dehydrogenase, their red blood cells cannot obtain sufficient NADPH through the pentose phosphate pathway, so it is difficult to maintain the reduced state of glutathione, thus showing that red blood cells are prone to rupture and hemolytic jaundice occurs. This phenomenon often occurs after eating broad beans (strong oxidizing agents) and is known as broad bean disease.
  • Glutathione has the effect of protecting the liver. GSH has antioxidant and detoxification effects, and the sulfhydryl group in GSH molecules is the active group, which is easy to combine with some drugs (such as paracetamol), toxins (such as free radicals, iodoacetic acid, mustard gas), heavy metals (lead, mercury, arsenic, etc.), and has an integrated detoxification effect. In particular, GSH in liver cells can participate in biological transformation, which can transform toxic substances in the body into harmless substances and be excreted out of the body. Therefore, GSH is considered to have a protective effect on the liver, and is often used to treat liver diseases such as alcoholism, cirrhosis, hepatitis, and fatty liver. In the adjuvant treatment of liver disease, under the guidance of doctors, glutathione tablets can be used to detoxify heavy metals, inhibit skin melanin formation, and play a whitening and anti-allergic role.
  • Glutathione also helps maintain normal immune system function. In recent years, a large number of studies have shown that GSH can promote the proliferation of lymphocytes and monocytes, and play an important role in anti-infection and inflammatory response.
  • Glutathione is beneficial for protecting eye vision. GSH helps to maintain the transparency of the cornea and lens and the repair and regeneration of their tissues, and is also commonly used in the treatment of cataracts, keratopathy, and retinopathy.
  • The sulfhydryl group of GSH has nucleophilic properties and can bind to exogenous electronophilic poisons (such as carcinogens or drugs, etc.), thereby blocking the binding of these substances with DNA, RNA or proteins to protect the body from toxicant damage.

Applications of Glutathione

The main characteristics of glutathione molecular structure are its free sulfhydryl group and strong ability to supply electron or protic hydrogen, and it can be used as a water-phase antioxidant and antioxidant cofactor to protect DNA, proteins and other biomolecules against oxidative damage. The structural characteristics of glutathione determine that it plays an important physiological function in living organisms, and is widely used in medicine, food and cosmetics industries.

Application of Glutathione in Food

Glutathione has been widely used in various fields of food processing, and it is mainly used to inhibit Browning, prolong food storage period, and increase food flavor.

Application of Glutathione in Whitening Field

The color of the skin depends on the ratio of two different types of melanin in the skin, namely the dark brown eumelanin and the yellow-red phaeomelanin. Glutamine acts as a skin whitening agent by inhibiting tyrosinase, which helps in the formation of melanin. It also converts eumelanin to fusomelanin, which causes the skin to turn white. It has become a popular skin whitening agent, and even dermatologists use it to treat melasma and other facial melanosis

Application of Glutathione in Medical Field

In view of the multiple roles of glutathione in cell physiology, clinical studies to alter glutathione homeostasis have also received attention. The list of conditions associated with impaired glutathione homeostasis continues to grow and reflects the importance and diversity of glutathione cell function. Diseases associated with glutathione include neurodegenerative diseases (particularly Parkinson's and Alzheimer's diseases), lung diseases (chronic obstructive pulmonary disease, asthma, and acute respiratory distress syndrome), cystic fibrosis, immune diseases (HIV, autoimmune diseases), cardiovascular diseases (hypertension, myocardial infarction, cholesterol oxidation), And age-related oxygen-related diseases (such as cataracts, macular degeneration, hearing impairment, and glaucoma), as well as the aging process itself.

Application of Glutathione in Dietary Supplement Field

Under the federal Food, Drug, and Cosmetic Act issued by the US Food and Drug Administration (US-FDA), glutathione-based oral dietary supplements are generally not restricted in the United States. Since free radicals play an important role in the development of age-related diseases, GSH is considered an effective anti-aging drug due to its outstanding antioxidant properties. Maintaining optimal GSH levels in different tissues is considered an important strategy for preventing oxidative stress-related diseases.

Reference

  1. Paul, N.B.; et al. Gamma-Glutamyl Transferase (γ-GT) – an old dog with new tricks? Liver International. 2022, 42(1): 9-15.
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