Effects of oleoyl-CoA on the activity and functional state of UDP-glucuronosyltransferase.
Addition of oleoyl-CoA to microsomes inhibited UDP-glucuronosyltransferase (assayed with 1-naphthol or p-nitrophenol) at concentrations within the physiologic range of total long-chain acyl-CoAs in liver. Inhibition of activity was associated with changes in the regulatory properties of the enzyme indicating that oleoyl-CoA altered the functional state of UDP-glucuronosyltransferase. The effect of oleoyl-CoA on the state of UDP-glucuronosyltransferase depended on the concentration of oleoyl-CoA, whether oleoyl-CoA was added in the presence or absence of substrates, the duration of treatment with oleoyl-CoA, and the aglycone with which activity was assayed. When oleoyl-CoA was added to microsomes in the presence of aglycones or UDP-glucuronic acid, inhibition by oleoyl-CoA was reversed by albumin, which by itself had no effect on activity. But UDP-glucuronosyltransferase, assayed with either aglycone, did not revert to the native state on removing oleoyl-CoA. Instead sequential treatment with oleoyl-CoA and albumin, in the presence of at least one substrate, produced a form of UDP-glucuronosyltransferase that was more active than the native state. When oleoyl-CoA was added to microsomes in the absence of aglycones or UDP-glucuronic acid, the activity of enzymes assayed with 1-naphthol decayed irreversibly to zero. Similar treatment followed by assay with p-nitrophenol as aglycone led to an active form of the enzyme that was inhibited further by albumin. The data are compatible with the idea that long-chain acyl-CoAs could regulate the functional state of UDP-glucuronosyltransferase.
Division of Digestive Diseases, Cornell University Medical College, New York, NY 10021.
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D000214:Acyl Coenzyme A / Q000378:metabolism / Q000494:pharmacology*; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002793:Cholic Acids / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009284:Naphthols; D009596:Nitrophenols; D051381:Rats; D017208:Rats, Wistar
D000214:Acyl Coenzyme A; D000418:Albumins; D002793:Cholic Acids; D009284:Naphthols; D009596:Nitrophenols; C017585:oleoyl-coenzyme A; C029350:1-naphthol; D014453:Glucuronosyltransferase; C024836:4-nitrophenol