What is Glutathione?

Introduction

Glutathione (γ-Glu-Cys-Gly, GSH) is the most abundant antioxidant in animal tissues, at 0.1-10 mM, as well as in plants and microorganisms. Glutathione exists in two different forms: reduced (GSH) and oxidized (glutathione disulfide, GSSG), with GSH being the predominant form intracellularly. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H⁺ + e^-) to other molecules, such as reactive oxygen species to neutralize them, or to protein cysteines to maintain their reduced forms. With donating an electron, glutathione itself becomes reactive and readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is probable due to the relatively high concentration of glutathione in cells (up to 7 mM in the liver).

Glutathione Synthesis

Most tissues (including oral mucosal cells) have the capability to synthesize GSH. Glutathione is synthesized in two sequential ATP-dependent enzymatic reactions that are catalyzed by γ-glutamylcysteine synthetase (γ-GCS, EC 6.3.2.2) and GSH synthetase (GS, EC 6.3.2.3). Both enzymes are exclusively cytosolic. γ-GCS is a heterodimeric enzyme catalyzing the first and rate-limiting step and GS apparently has no regulatory role. γ-GCS is composed of a catalytic subunit and a regulatory subunit. The catalytic subunit contributes all of enzymatic activity and is feedback-inhibited by GSH. The rate of glutathione synthesis is also dependent on cysteine availability. The intracellular glutamate concentration is several-fold higher than the Km value of γ-GCS for glutamate, while the intracellular cysteine concentration approximates the Km value for cysteine (0.1-0.3 mM).

Function

Glutathione provides cells with its reducing properties, maintains cysteine residues in proteins in their reduced form, and protects against the constant assault of oxidative stress. The distinct γ-linkage between glutamic acid and cysteine is thought to protect the tripeptide from degradation of aminopeptidases. In addition, glutathione is also less prone to oxidation than cysteine. These make glutathione an ideal compound for maintaining intracellular redox potential. Its many functional roles include the detoxification of a variety of endogenous and exogenous compounds such as xenobiotics, free radicals and lipid peroxides, preservation of protein structure and function, regulation of protein synthesis and degradation and modulation of immune function. So glutathione plays an important role in preventing oxidative damage to the skin. In addition to its many recognized biological functions, glutathione has also been associated with skin lightening ability. The role of glutathione as a skin whitener was discovered as a side effect of large doses of glutathione. Its antioxidant property also protects the skin from UV radiation and other environmental as well as internal stressors that generate free radicals that cause skin damage and hyperpigmentation. 

Glutathione and Related Disease

Glutathione deficiency is associated with many human diseases, such as diabetes, alcoholic liver disease, acquired immunodeficiency syndrome (AIDS) and cataract. A decrease of glutathione levels is also found in aging organisms including rodents, insects and humans. Glutathione deficiency is suggested to be associated with high risk of cancers including oral cancer. Although glutathione deficiency has been linked to a high risk of cancers, ironically, high levels of glutathione are often found in tumors.

Reference:

Huang, Zhishan. Inhibition of Caspase Activity by Protein Glutathiolation in Oral Tumor Cells. ProQuest, 2005.