Role of glutathione in the regulation of hepatic cholesterol 7α-hydroxylase, the rate-limiting enzyme of bile acid biosynthesis

Aslam S. Hassan, Judy J. Hackley, Elizabeth H. Jeffery

Research output: Contribution to journalArticle

Abstract

The effect of in vivo variation of hepatic glutathione (using diethyl maleate and L-cysteine) on in vitro cholesterol 7α-hydroxylase activity was studied in male Sprague-Dawley rats. Cholesterol 7α-hydroxylase activity in glutathione-depleted rats (ca. 10% of control glutathione) was significantly reduced compared to that in vehicle-injected controls. While L-cysteine treatment of glutathione-depleted animals increased glutathione levels somewhat (ca. 20% of control glutathione), they were still significantly less than control levels. Similarly, cholesterol 7α-hydroxylase activity in the partially glutathione replete animals was approximately 50% greater than that in the glutathione-depleted animals, but still significantly less than that in the controls. The rate of 7α-hydroxylation of cholesterol was found to be dependent on liver glutathione content. The calculated maximal rate was 34.4 picomoles/mg/min with a half maximal activity at 1.89 μmoles glutathione/gm liver. These results suggest that hepatic glutathione may be an important modulator of in vivo activity of cholesterol 7α-hydroxylase.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalSteroids
Volume44
Issue number4
DOIs
StatePublished - Oct 1984

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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