Glutathione Conjugate Transport in Hepatic Elimination of Electrophiles

Abstract

Glutathione has several functions in liver and in the organism. This tripeptide is of interest regarding the hepatic elimination of drugs, subsequent to the formation of glutathione S-conjugates. The reaction is catalysed by glutathione S-transferases in the first step of mercapturic acid biosynthesis (Boyland and Chasseaud, 1969; Jacoby, 1978; Levine, 1978). These thioethers in general are less toxic and more water-soluble than the original foreign compound and are eliminated via the bile, since the S-conjugates are anions with a molecular weight exceeding 300 (Chasseaud, 1974). The glutathione S-conjugates generated from the glutathione S-transferase reactions are also eliminated from many other types of cell in the organism. A sufficient capacity for transport of glutathione conjugates is required not only for the inter-organ relationships regarding mercapturate formation, but also for the maintenance of a low intracellular steady state concentration of these compounds, as glutathione S-conjugates have potentially harmful effects. The present article focuses on the competition of glutathione conjugates with other transport systems at the cell surface (Akerboom et al, 1982) as well as with site in the interior of the cell such as the inhibition of glutathione reductase (Bilzer et al, 1984).KeywordsGlutathione ReductaseGlutathione DisulfideButhionine SulfoximineDiethyl MaleateGSSG ReductaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.