Dietary modulation of the glutathione detoxification pathway and the potential for altered xenobiotic metabolism.
This review summarizes the literature regarding nutritional regulation of the pathways of glutathione synthesis and subsequent conjugation of xenobiotic compounds. The glutathione detoxification pathway includes the enzymes of the gamma-glutamyl cycle as well as sulfur conjugation reactions. This promotes bodily excretion of xenobiotics as well as normal metabolites. Regulation of intracellular glutathione concentrations is maintained largely through changes in the activity of gamma-glutamylcysteine synthetase. Availability of glutathione for detoxification purposes can be limited by the supply of intracellular cysteine to serve as a precursor for glutathione synthesis through the gamma-glutamyl cycle. Dietary methionine, cysteine and cysteine prodrugs have been examined for their potential to maximize glutathione availability for detoxification purposes. Some xenobiotic challenges have been reported to deplete hepatic glutathione reserves and toxicity correlates with the degree of depletion. Other foreign compounds, however, have been observed to increase cellular glutathione concentrations beyond normal levels despite regulation of the synthetic pathway. Such effects will be reviewed.
Smith
T K
TK
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
D000818:Animals; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D015262:Xenobiotics / Q000633:toxicity*
D015262:Xenobiotics; D005978:Glutathione