Characterization of rat liver bile acid acyl glucuronosyltransferase

Nariyasu Mano, Koji Nishimura, Takashi Narui, Shigeo Ikegawa, Junichi Goto

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Recent studies have suggested that bile acid acyl glucuronides form covalently bound protein adducts which may cause hypersensitivity reactions and increased morbidity in patients. Although the preferential biosynthesis of the acyl glucuronides has been known, the characterization of hepatic bile acid acyl glucuronosyltransferase has not yet been clearly elucidated. We have investigated the substrate specificity of the hepatic bile acid acyl glucuronosyltransferase using five common bile acids as substrates. The glucuronidation rate was dependent on the number of the hydroxy group on the steroid nucleus and mono-hydroxylated lithocholic acid, the more lipophilic common bile acid, was most effectively metabolized into its acyl glucuronide. The tri-hydroxylated cholic acid, the more water-soluble common bile acid, barely transformed into its glucuronide. Results showed decreasing of the initial velocity of the acyl glucuronidation with increasing of the concentration of substrate, lithocholic acid, owing to the substrate inhibition of the hepatic bile acid acyl glucuronosyltransferase. The substrate analogues, glycine and taurine conjugated bile acids, which exist in the body fluids in high concentrations, also inhibited the enzyme's activity. In addition, enzymatic reaction products, bile acid acyl glucuronides, also inhibited the activity. These inhibitory mechanisms may be responsible for the low concentration of bile acid acyl glucuronides in urine and may be an important detoxification system in the body.

本文言語English
ページ(範囲)257-262
ページ数6
ジャーナルSteroids
67
3-4
DOI
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 内分泌学
  • 薬理学
  • 臨床生化学
  • 有機化学

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