Sulphoxide reduction by rat intestinal flora and by Escherichia coli in vitro.
The caecal microflora from female rats show a greater ability to reduce the sulphoxide group of sulindac than either the liver or kidneys. Studies on sulphoxide reduction by Escherichia coli showed that NADH, NADPH and dithiothreitol (DTT), but not acetaldehyde could act as cofactors. The cytosolic fraction was responsible for about 90%, 80% and 60% of the total reducing activity with sulindac, diphenyl sulphoxide and sulphinpyrazone, respectively. The main NADPH linked activity in the E. coli cytosol was dependent on thioredoxin, since the activity was essentially abolished by passing through a G50 column or by the addition of anti-thioredoxin anti-serum. Partial purification and separation of sulphoxide reducing activity by DEAE-cellulose chromatography separated two main protein bands, each of which possessed sulindac reducing activity. The importance of thioredoxin for much of the NADPH dependent activity was confirmed but the eluate fractions also showed the presence of other activities with NADH, NADPH and DTT that were independent of thioredoxin. Incubation of the DEAE-cellulose eluate fractions with flosequinan and sulphinpyrazone showed that the reducing activity in the two main protein peaks showed different substrate specificities and that there were multiple sulphoxide reductase systems present in E. coli cytosol.
Lee
S C
SC
University of Southampton, U.K.
Renwick
A G
AG
D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism; D002432:Cecum / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004229:Dithiothreitol / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D066298:In Vitro Techniques; D007422:Intestines / Q000382:microbiology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010088:Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D051381:Rats; D013379:Substrate Specificity; D013442:Sulfinpyrazone / Q000378:metabolism; D013467:Sulindac / Q000378:metabolism; D013879:Thioredoxins / Q000276:immunology / Q000494:pharmacology; D015262:Xenobiotics / Q000378:metabolism
D001555:Benzene Derivatives; D015262:Xenobiotics; D013467:Sulindac; C048860:diphenyl sulfoxide; D013879:Thioredoxins; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C030542:sulfoxide reductase; D004229:Dithiothreitol; D013442:Sulfinpyrazone