oleoyl-coenzyme-a and 1-naphthol

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.

Topics: Acyl Coenzyme A; Albumins; Animals; Cholic Acids; Enzyme Activation; Glucuronosyltransferase; Kinetics; Male; Microsomes, Liver; Naphthols; Nitrophenols; Rats; Rats, Wistar