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Glucuronidation of bile acids by rat liver 3-OH androgen UDP-glucuronyltransferase.

1984; Elsevier BV; Volume: 259; Issue: 10 Linguagem: Inglês

10.1016/s0021-9258(20)82122-x

1083-351X

Robert B. Kirkpatrick, Charles N. Falany, Thomas R. Tephly,

Aldose Reductase and Taurine

The glucuronidation of bile acids is an important pathway for the detoxificaton and elimination of retained bile acids during cholestasis.A 3-OH-specific androgen UDP-glucuronyltransferase was purified from solubilized female rat liver microsomes using Chromatofocusing and UDP-hexanolamine-Sepharose 4B affinity chromatography.The purified 3-OH androgen UDP-glucuronyltransferase is reactive towards bile acids, including lithocholic acid, deoxycholic acid, and ursodeoxycholic acid, in addition to the androgenic steroids etiocholanolone and androsterone.The highest activity towards bile acids is seen with lithocholic acid-24-methyl ester, and no activity is seen with lithocholic acid-3a-sulfate or B@-cholanic acid-3-one.No glucuronidation activity towards bile acids was observed with either a purified 17-OH steroid UDP-glucuronyltransferase or a p-nitrophenol-UDP-glucuronyltransferase.Lithocholic acid competitively inhibits etiocholanolone glucuronidation by the purified 3-OH androgen isoenzyme.These results suggest that a UDP-glucuronyltransferase isoenzyme is present in female rat liver which is capable of specifically glucuronidating the 3-OH group of bile acids and androgenic steroids.Bile acids are synthesized in the liver and, under physiologic conditions, are an important pathway for the excretion of cholesterol, maintenance of bile flow, and facilitation of fat digestion in the small intestine (1).Cholestasis impairs bile flow, and bile acid disposition is altered such that sulfate and glucuronide conjugates of these substances are increased in the urine and plasma (2-4).It has been suggested that these conjugation reactions provide an important means for elimination of the retained bile acids which might be expected to exert hepatotoxicity (5,6).Hepatic UDP-glucuronyltransferase activities capable of reacting with drugs and steroids have been studied extensively in recent years (7-9).There has been a clear demonstration of separate isoenzymes in rabbit liver responsible for the glucuronidation of estrone and p-nitrophenol (10).In addition, there have been numerous other studies which suggest * This work was