| First Author | Autio KJ | Year | 2014 |
| Journal | Biochem J | Volume | 461 |
| Issue | 1 | Pages | 125-35 |
| PubMed ID | 24735479 | Mgi Jnum | J:213609 |
| Mgi Id | MGI:5585380 | Doi | 10.1042/BJ20130915 |
| Citation | Autio KJ, et al. (2014) Role of AMACR (alpha-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice. Biochem J 461(1):125-35 |
| abstractText | Cholesterol is catabolized to bile acids by peroxisomal beta-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 (alpha-methylacyl-CoA racemase) or MFE-2 (peroxisomal multifunctional enzyme type 2), in which this beta-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. |
