Cyp3a11 is not essential for the formation of murine bile acids

Annika Wahlström; Samer Al-Dury; Marcus Ståhlman; Fredrik Bäckhed; Hanns-Ulrich Marschall

doi:10.1016/j.bbrep.2017.02.011

Cyp3a11 is not essential for the formation of murine bile acids

Annika Wahlström, Samer Al-Dury, Marcus Ståhlman, Fredrik Bäckhed, Hanns-Ulrich Marschall

8 Citations (Scopus)

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Abstract

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 theCyp3a11gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles inCyp3adeficient mice, which lack 7 genes in theCyp3agene cluster includingCyp3a11, and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum fromCyp3aknock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition.We concludethatCyp3a11is not necessary for 6β-hydroxylation and the formation of MCAs.

Original language	English
Journal	Biochemistry and Biophysics Reports
Volume	10
Pages (from-to)	70-75
Number of pages	6
ISSN	2405-5808
DOIs	https://doi.org/10.1016/j.bbrep.2017.02.011
Publication status	Published - 1 Jul 2017

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Cyp3a11 is not essential for the formation of murine bile acidsFinal published version, 619 KBLicence: CC BY-NC-ND

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@article{62c0493bf27c4af38c3cff57a60034bf,

title = "Cyp3a11 is not essential for the formation of murine bile acids",

abstract = "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 theCyp3a11gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles inCyp3adeficient mice, which lack 7 genes in theCyp3agene cluster includingCyp3a11, and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum fromCyp3aknock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition.We concludethatCyp3a11is not necessary for 6β-hydroxylation and the formation of MCAs.",

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author = "Annika Wahlstr{\"o}m and Samer Al-Dury and Marcus St{\aa}hlman and Fredrik B{\"a}ckhed and Hanns-Ulrich Marschall",

year = "2017",

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doi = "10.1016/j.bbrep.2017.02.011",

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T1 - Cyp3a11 is not essential for the formation of murine bile acids

AU - Wahlström, Annika

AU - Al-Dury, Samer

AU - Ståhlman, Marcus

AU - Bäckhed, Fredrik

AU - Marschall, Hanns-Ulrich

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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 theCyp3a11gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles inCyp3adeficient mice, which lack 7 genes in theCyp3agene cluster includingCyp3a11, and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum fromCyp3aknock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition.We concludethatCyp3a11is not necessary for 6β-hydroxylation and the formation of MCAs.

AB - 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 theCyp3a11gene would lack MCAs. To test this hypothesis, we analyzed bile acid profiles inCyp3adeficient mice, which lack 7 genes in theCyp3agene cluster includingCyp3a11, and compared them with wild-type littermate controls. Bile acid composition in liver, gallbladder, caecum and serum fromCyp3aknock out mice and wild-type littermate controls was analyzed with UPLC-MS/MS and revealed no major differences in bile acid composition.We concludethatCyp3a11is not necessary for 6β-hydroxylation and the formation of MCAs.

KW - Journal Article

U2 - 10.1016/j.bbrep.2017.02.011

DO - 10.1016/j.bbrep.2017.02.011

M3 - Journal article

C2 - 28955737

SN - 2405-5808

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SP - 70

EP - 75

JO - Biochemistry and Biophysics Reports

JF - Biochemistry and Biophysics Reports

ER -

Cyp3a11 is not essential for the formation of murine bile acids

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