Glutahione is the most abundant non-proteic thiol in cells (Jocelyn, 1973). Its intracellular concentration is around 5 mmols per gram of tissue, i.e. similar to that of glucose in cells (Viña et al. 1978). Glutathione was discovered in the late 19^th century by deRey-Pailhade (1888) in Montpellier, France. Its structure was studied by Hopkins who thought that it was a dipeptide composed of glutamate an cysteine. Harrington and Mead, in 1935 finally described the correct structure of the tripeptide: gamma-glutamyl cysteinyl glycine. The name glutathione was introduced by Hopkins in 1921. An excellent review on historical aspects of the discovery of glutathione was published by Meinster (1988).

Work on glutathione was greatly boosted after a critical paper in Nature by E.M. & N.S. Kosower (1969). The title of that paper “Lest I forget thee glutathione” indicates the relatively scarce numbers of papers published on glutathione on those days. Research on this molecule boasted thereafter and over 40000 papers have been published on this molecule (Sies 1999). Books on glutathione have also been published (Viña, 1990).

Meinster, who contributed significantly to the understanding of the enzymology and physiological functions of glutathione published a comprehensive review on this topic in 1983.

Glutathione has many physiological functions. They are derived from its peculiar chemical characteristics: the gamma-glutamyl bond between the glutamate and cysteine residues and the presence of the free thiol group. This latter characteristic, given the high concentration of the reduced form of glutathione (GSH) and the presence of enzymes catalysing the oxidation of glutathione (glutathione peroxidases) and tis reduction (glutathione reductases) make glutathione one of the best redox buffers in cells.

The level of GSH in cells is very high (i.e. in the millimolar range). The level of te oxidised form, GSSG, is significantly lower. The level of GSH/GSSG ratio is around ten to one hundred. If one assumes that the glutathione reductase is at equilibrium in vivo and given the well known NADP/NADPH ratio in the cytosol and the equilibrium constant for the glutathione reductase, the GSH/GSSG ratio should be even higher, closer to 10000 (Viña et al. 1978). However, after considerable experimental care, ratios of this order are not found. Thus, we may conclude that glutathione reductase may not be at equilibrium in vivo (Viña et al. 1978).  

Briefly, glutathione is the most abundant non-protein thiol in cells. It is a tripeptide with two important structural features: the thiol group and the gamma-glutamyl peptide bond between glutamate and cysteine. It is a major antioxidant, able to reduce peroxides (due to its action as substrate of glutathione peroxidases). As a result it is oxidised to the disulphide form (GSSG), which in turn is reduced back to GSH by glutathione reductase. Thus glutathione is a major player in  maintaining physiological redox status in cells. 

Some of the functions of glutathione depend on the presence of the gamma-glutamyl bond, for instance its role in the regulation of amino acid transport. But the majority of the functions of glutathione are related to its role in redox regulation in cells and in detoxification of xenobiotics.

Some areas of research of special interest on this molecule are glutathionylation of proteins, the cellular compartmentation and the role of this interesting molecule in disease.