Intestinal glutathione transport system: a possible detoxication role.
The epithelium of the small intestine act by the formation of GSH-S-conjugation, as a first line of defence against various ingested toxic chemicals. GSH and GSH-dependent enzymes are present in the gastrointestinal wall. We and others have characterized the GSH-specific transport systems in intestinal brush-border and in basolateral membrane vesicles, in which gamma-glutamyltranspeptidase (gamma-GT) activity was inactivated by AT-125. In the present study we use inhibition experiments, kinetic studies, trans-stimulation of GSH uptake and HPLC determination to demonstrate (for the first time) that GSH and two GSH-S-conjugates (chosen as model compounds) share a common transport system. Plasma GSH-S-conjugates that may enter the intestinal cells via basolateral membrane, and GSH-S-conjugates that form in intestinal cells, may be eliminated directly by this GSH transporter across brush-border membranes or transported into lumen to the active site of gamma-GT; they are then further metabolized and excreted by various routes. This transport system may thus contribute to the intestinal detoxication role.
Vincenzini
M T
MT
Department of Biochemical Sciences, University of Florence, Italy.
Favilli
F
F
Stio
M
M
Iantomasi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism* / Q000502:physiology; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D011817:Rabbits
C038391:S-(4-nitrobenzyl)glutathione; C042431:S-ethyl glutathione; D005982:Glutathione Transferase; D005978:Glutathione