Synthesis of atypical bile acids for use as investigative tools for the genetic defect of 3β-hydroxy-Δ(5)-C27-steroid oxidoreductase deficiency

J Steroid Biochem Mol Biol. 2014 Oct:144 Pt B:348-60. doi: 10.1016/j.jsbmb.2014.06.008. Epub 2014 Jun 19.


Deficiency of 3β-hydroxy-Δ(5)-C27-steroid oxidoreductase (HSD3B7), an enzyme catalyzing the second step in the pathway for bile acid synthesis, leads to a complete lack of the primary bile acids, cholic and chenodeoxycholic acids, and the accumulation of 3β,7α-dihydroxy- and 3β,7α,12α-trihydroxy-Δ(5)-cholenoic acids. Patients affected by this autosomal recessive genetic defect develop cholestatic liver disease that is clinically responsive to primary bile acid therapy. Reference standards of these compounds are needed to facilitate diagnosis and to accurately quantify biochemical responses to therapy. Described are a novel synthesis of atypical bile acids that characterize the HSD3B7 deficiency and their effect on bile acid-activated nuclear receptors, target genes and cytochromes involved in bile acid homeostasis and detoxification. The failure of 3β-hydroxy-Δ(5)-cholenoic acids to function as FXR, PXR and CAR agonists and to exert hepatoprotective actions explains the mechanism for progressive cholestatic liver disease in patients with HSD3B7 deficiency.

Keywords: 3β-Hydroxy-Δ5-C27-steroid oxidoreductase; Bile acids; Biomarkers; Diagnosis; Gene expression; Inborn errors; Mass spectrometry; Nuclear receptors; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital / genetics
  • Adrenal Hyperplasia, Congenital / metabolism*
  • Bile Acids and Salts / chemical synthesis
  • Bile Acids and Salts / pharmacology*
  • Constitutive Androstane Receptor
  • Hep G2 Cells
  • Humans
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism*


  • Bile Acids and Salts
  • Constitutive Androstane Receptor
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • farnesoid X-activated receptor

Supplementary concepts

  • Adrenal hyperplasia 2