The enzymes, regulation, and genetics of bile acid synthesis

Research output: Contribution to journalArticle

988 Citations (Scopus)

Abstract

The synthesis and excretion of bile acids comprise the major pathway of cholesterol catabolism in mammals. Synthesis provides a direct means of converting cholesterol, which is both hydrophobic and insoluble, into a water-soluble and readily excreted molecule, the bile acid. The biosynthetic steps that accomplish this transformation also confer detergent properties to the bile acid, which are exploited by the body to facilitate the secretion of cholesterol from the liver. This role in the elimination of cholesterol is counterbalanced by the ability of bile acids to solubilize dietary cholesterol and essential nutrients and to promote their delivery to the liver. The synthesis of a full complement of bile acids requires 17 enzymes. The expression of selected enzymes in the pathway is tightly regulated by nuclear hormone receptors and other transcription factors, which ensure a constant supply of bile acids in an ever changing metabolic environment. Inherited mutations that impair bile acid synthesis cause a spectrum of human disease; this ranges from liver failure in early childhood to progressive neuropathy in adults.

Original languageEnglish (US)
Pages (from-to)137-174
Number of pages38
JournalAnnual Review of Biochemistry
Volume72
DOIs
StatePublished - 2003

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Bile Acids and Salts
Enzymes
Cholesterol
Liver
Dietary Cholesterol
Mammals
Liver Failure
Cytoplasmic and Nuclear Receptors
Genetics
Detergents
Nutrients
Transcription Factors
Food
Mutation
Molecules
Water

Keywords

  • Catabolism
  • Cholesterol
  • Cytochrome P450
  • Genetic disease
  • Nuclear receptors

ASJC Scopus subject areas

  • Biochemistry

Cite this

The enzymes, regulation, and genetics of bile acid synthesis. / Russell, David W.

In: Annual Review of Biochemistry, Vol. 72, 2003, p. 137-174.

Research output: Contribution to journalArticle

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