Glutathione S-transferase in mucus of rat small intestine.
Glutathione S-transferases in the small intestine function in detoxification of electrophilic compounds ingested in foods, dietary supplements, and orally administered drug preparations. Although the required substrate glutathione (GSH) is synthesized in the intestinal enterocytes, the rate of synthesis is slow compared to both the maximal GST activity and the rate of uptake of luminal GSH. GSH is supplied to the intestinal lumen in the bile, and normal luminal concentrations in the rat are about 250 microM. The present study was designed to test the hypothesis that exogenous GSH is used for intestinal conjugation by glutathione S-transferase. The results show that 250 microM of extracellular GSH stimulated conjugation of 1-chloro-2,4-dinitrobenzene by approximately 300% in rat intestinal enterocyte preparations. However, an unexpected finding was that most of this stimulated activity did not depend upon uptake of GSH by the enterocytes but was due to glutathione S-transferase associated with mucus. Immunohistochemistry of glutathione S-transferase in the intact small intestine confirmed that a portion of the GST is present in the mucus layer. The presence of this detoxication enzyme in the extracellular mucus layer provides a novel mechanism for preventing direct contact of potentially toxic dietary electrophiles with the intestinal enterocytes.
Samiec
P S
PS
Department of Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
Dahm
L J
LJ
Jones
D P
DP
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002469:Cell Separation; D004137:Dinitrochlorobenzene / Q000493:pharmacokinetics; D020895:Enterocytes / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology*; D008297:Male; D009093:Mucus / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004137:Dinitrochlorobenzene; D005982:Glutathione Transferase; D005978:Glutathione