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

Kaija J. Autio*, Werner Schmitz, Remya R. Nair, Eija M. Selkäl̈a, Raija T. Sormunen, Ilkka J. Miinalainen, Peter J. Crick, Yuqin Wang, William J. Griffiths, Janardan K. Reddy, Myriam Baes, J. Kalervo Hiltunen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalBiochemical Journal
Issue number1
StatePublished - Jul 1 2014


  • Bile acid
  • Peroxisomal multifunctional enzyme 1 (MFE-1)
  • Peroxisome
  • α-methylacyl-CoA racemase (AMACR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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