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Cyp3a11 is not essential for the formation of murine bile acids

Artikel i vetenskaplig tidskrift
Författare Annika Wahlström
Samer Al-Dury
Marcus Ståhlman
Fredrik Bäckhed
Hanns-Ulrich Marschall
Publicerad i Biochemistry and Biophysics Reports
Volym 10
Sidor 70-75
ISSN 2405-5808
Publiceringsår 2017
Publicerad vid Wallenberglaboratoriet
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 70-75
Språk en
Länkar dx.doi.org/10.1016/j.bbrep.2017.02....
Ämnesord 6-Hydroxylation, FXR, Mouse models, P450 enzymes
Ämneskategorier Biokemi och molekylärbiologi

Sammanfattning

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 Cyp3a11 gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles in Cyp3a deficient mice, which lack 7 genes in the Cyp3a gene cluster including Cyp3a11, and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum from Cyp3a knock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition. We conclude that Cyp3a11 is not necessary for 6β-hydroxylation and the formation of MCAs. © 2017 The Authors

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