Metabolism and functions of glutathione in brain

The tripeptide glutathione is the thiol compound present in the highest con centration in cells of all organs. Glutathione has many physiological funct ions including its involvement in the defense against reactive oxygen speci es. The cells of the human brain consume about 20% of the oxygen utilized b y the body but constitute only 2% of the body weight. Consequently, reactiv e oxygen species which are continuously generated during oxidative metaboli sm will be generated in high rates within the brain. Therefore. the detoxif ication of reactive oxygen species is an essential task within the brain an d the involvement of the antioxidant glutathione in such processes is very important. The main focus of this review article will be recent results on glutathione metabolism of different brain cell types in culture. The glutat hione content of brain cells depends strongly on the availability of precur sors for glutathione. Different types of brain cells prefer different extra cellular glutathione precursors. Glutathione is involved in the disposal of peroxides by brain cells and in the protection against reactive oxygen spe cies. In coculture astroglial cells protect other neural cell types against the toxicity of various compounds. One mechanism for this interaction is t he supply by astroglial cells of glutathione precursors to neighboring cell s. Recent results confirm the prominent role of astrocytes in glutathione m etabolism and the defense against reactive oxygen species in brain. These r esults also suggest an involvement of a compromised astroglial glutathione system in the oxidative stress reported for neurological disorders. (C) 200 0 Elsevier Science Ltd. All rights reserved.