Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice

Biochem J. 2014 Jul 1;461(1):125-35. doi: 10.1042/BJ20130915.


Cholesterol is catabolized to bile acids by peroxisomal β-oxidation in which the side chain of C27-bile acid intermediates is shortened by three carbon atoms to form mature C24-bile acids. Knockout mouse models deficient in AMACR (α-methylacyl-CoA racemase) or MFE-2 (peroxisomal multifunctional enzyme type 2), in which this β-oxidation pathway is prevented, display a residual C24-bile acid pool which, although greatly reduced, implies the existence of alternative pathways of bile acid synthesis. One alternative pathway could involve Mfe-1 (peroxisomal multifunctional enzyme type 1) either with or without Amacr. To test this hypothesis, we generated a double knockout mouse model lacking both Amacr and Mfe-1 activities and studied the bile acid profiles in wild-type, Mfe-1 and Amacr single knockout mouse line and Mfe-1 and Amacr double knockout mouse lines. The total bile acid pool was decreased in Mfe-1-/- mice compared with wild-type and the levels of mature C24-bile acids were reduced in the double knockout mice when compared with Amacr-deficient mice. These results indicate that Mfe-1 can contribute to the synthesis of mature bile acids in both Amacr-dependent and Amacr-independent pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / biosynthesis*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / physiology*
  • Racemases and Epimerases / deficiency
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • Bile Acids and Salts
  • Ehhadh protein, rat
  • Multienzyme Complexes
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase