Cyp3a11 is not essential for the formation of murine bile acids

• Published in: Biochemistry and biophysics reports 2017-07, Vol.10 (C), p.70-75
• Main Authors: Wahlström, Annika, Al-Dury, Samer, Ståhlman, Marcus, Bäckhed, Fredrik, Marschall, Hanns-Ulrich
• Format: Article
• Language: English
• Subjects: 6-Hydroxylation; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; FXR; Mouse models; P450 enzymes
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2017.02.011

Humans and mice differ substantially in their bile acid profiles as mice in addition to cholic acid (CA) predominantly synthesize 6β-hydroxylated muricholic acids (MCAs) whereas humans produces chenodeoxycholic acid (CDCA) and CA as primary bile acids. Identifying the gene performing 6β-hydroxylation would be useful for 'humanizing' the bile acid profile in mice for studies of the interaction between bile acids, gut microbiota, and host metabolism. We investigated the formation of MCAs in primary murine hepatocytes and found that αMCA is synthesized from CDCA and βMCA from UDCA. It is commonly assumed that the P450-enzyme CYP3A11 catalyzes 6β-hydroxylation of bile acids, thus we hypothesized that mice without the gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles in deficient mice, which lack 7 genes in the gene cluster including , and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum from knock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition. that is not necessary for 6β-hydroxylation and the formation of MCAs.