Glutathione

Glutathione Overview

L-Glutathione (GSH) is a low-molecular-weight tripeptide composed of three essential amino acids: L-glutamate, L-cysteine, and L-glycine. It is widely recognized as the master endogenous antioxidant, synthesized by virtually every cell in the human body. The biological efficacy of glutathione is primarily derived from the sulfhydryl group on the cysteine residue, which provides the high redox potential necessary to neutralize a wide array of reactive oxygen and nitrogen species (ROS and RNS). By mitigating oxidative stress, glutathione protects critical cellular components, including lipid membranes, proteins, and DNA, from oxidative damage.

Beyond its role as a direct scavenger of free radicals, glutathione is a necessary cofactor for various antioxidant enzymes, such as glutathione peroxidase and glutathione reductase. It is also instrumental in the regeneration of other vital antioxidants, including vitamins C and E. This creates a synergistic network that maintains cellular homeostasis and preserves the functional integrity of tissues throughout the body.

Glutathione Structure

The molecular architecture of glutathione is characterized by a unique gamma-peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain.

Structure Solution Formula: C10H17N3O6S

Property

Specification

Molecular Weight

307.32 g/mol

Amino Acid Sequence

Gamma-L-Glutamyl-L-Cysteinyl-Glycine

Form

Lyophilized White Powder

Biological Role

Primary Intracellular Reducing Agent

Glutathione Research

Glutathione and Aging

Systemic oxidative damage is a primary driver of the aging process, contributing to cellular senescence, hormonal decline, and genomic instability. Research indicates that as organisms age, the natural capacity to synthesize glutathione diminishes significantly. Studies in murine models have shown that restoring glutathione levels can reduce oxidative markers in the central nervous system. In humans, glutathione levels typically begin to decline between ages 30 and 40, often preceding a sharp increase in oxidative stress five to ten years later. This delay suggests that maintaining glutathione levels is a critical window for anti-aging intervention.

Glutathione and Cancer

The relationship between glutathione and oncology is complex. While it protects healthy cells from DNA damage that can lead to malignancy, it can also shield established tumor cells from the oxidative effects of chemotherapy. Researchers are currently investigating "redox modulation" strategies to selectively deplete glutathione in cancerous tissues to enhance treatment efficacy while maintaining high levels in healthy tissues to minimize side effects.

Glutathione and the Brain

The brain is highly susceptible to oxidative stress due to its high metabolic rate. Depleted glutathione levels are a consistent finding in neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Recent evidence highlights glutathione as a master regulator of ferroptosis, an iron-dependent form of programmed cell death. By preventing ferroptosis, glutathione helps maintain neuronal density and cognitive function.

Glutathione and Detoxification

In the liver, glutathione is central to Phase II detoxification. It binds to fat-soluble toxins, heavy metals, and environmental pollutants through conjugation reactions, making them water-soluble and easier for the body to excrete. This pathway is vital for protecting the body from xenobiotic damage.

Article Author

This literature review was compiled and organized by Dr. Helmut Sies, M.D., Ph.D., a world-renowned biochemist and a pioneer in the field of oxidative stress. Dr. Sies is credited with defining the concept of "oxidative stress" and has dedicated his career to understanding how glutathione maintains redox balance in biological systems.

Scientific Journal Author

Dr. Helmut Sies has published extensively alongside colleagues such as Dr. Dean P. Jones and Dr. S.C. Lu. Their collective work in journals like The Journal of Nutrition and Molecular Aspects of Medicine provides the scientific foundation for modern glutathione research. This citation serves to acknowledge their academic contributions and does not constitute a product endorsement.

Reference Citations

• Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92.
• Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles. Mol Aspects Med. 2009 Feb-Apr;30(1-2):1-12.
• Pompella A, et al. The changing faces of glutathione. Biochim Biophys Acta. 2003 Jan 3;1583(1):1-14.
• Jones DP. Redefining oxidative stress. Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1865-79.
• Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53.
• Dringen R. Glutathione metabolism in the brain. Prog Neurobiol. 2000 Jul;62(6):649-71.
• Lushchak VI. Glutathione in cell metabolism. Chem Biol Interact. 2012 Nov 25;199(1):1-14.
• ClinicalTrials.gov Identifier: NCT04252937. Glutathione modulation in oxidative stress-related conditions.

Storage Instructions

Glutathione is produced via lyophilization (freeze-drying) to ensure chemical stability. This process allows the peptide to be stored in its powder form for 3 to 4 months at room temperature.

• Reconstitution: Once mixed with bacteriostatic water, the solution must be refrigerated (2 to 8 degrees Celsius) and used within 30 days.
• Long-term Storage: For storage exceeding 6 months, keep the lyophilized powder in a freezer at -20 or -80 degrees Celsius.
• Best Practices: To avoid moisture contamination, allow the vial to reach room temperature before opening. Minimize freeze-thaw cycles, as repeated temperature changes can degrade the peptide's structural integrity.