http://purl.uniprot.org/citations/23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/23933573 | http://www.w3.org/2000/01/rdf-schema#comment | "11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediates glucocorticoid activation and is currently considered as therapeutic target to treat metabolic diseases; however, biomarkers to assess its activity in vivo are still lacking. Recent in vitro experiments suggested that human 11β-HSD1 metabolizes the secondary bile acid 7-oxolithocholic acid (7-oxoLCA) to chenodeoxycholic acid (CDCA) and minor amounts of ursodeoxycholic acid (UDCA). Here, we provide evidence from in vitro and in vivo studies for a major role of 11β-HSD1 in the oxidoreduction of 7-oxoLCA and compare its level and metabolism in several species. Hepatic microsomes from liver-specific 11β-HSD1-deficient mice were devoid of 7-oxoLCA oxidoreductase activity. Importantly, circulating and intrahepatic levels of 7-oxoLCA and its taurine conjugate were significantly elevated in mouse models of 11β-HSD1 deficiency. Moreover, comparative enzymology of 11β-HSD1-dependent oxidoreduction of 7-oxoLCA revealed that the guinea-pig enzyme is devoid of 7-oxoLCA oxidoreductase activity. Unlike in other species, 7-oxoLCA and its glycine conjugate are major bile acids in guinea-pigs. In conclusion, the oxidoreduction of 7-oxoLCA and its conjugated metabolites are catalyzed by 11β-HSD1, and the lack of this activity leads to the accumulation of these bile acids in guinea-pigs and 11β-HSD1-deficient mice. Thus, 7-oxoLCA and its conjugates may serve as biomarkers of impaired 11β-HSD1 activity."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.org/dc/terms/identifier | "doi:10.1194/jlr.m042499"xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Odermatt A."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Lavery G.G."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Penno C.A."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Schuster D."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Morgan S.A."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/author | "Vuorinen A."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/name | "J Lipid Res"xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/pages | "2874-2883"xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/title | "Impaired oxidoreduction by 11beta-hydroxysteroid dehydrogenase 1 results in the accumulation of 7-oxolithocholic acid."xsd:string |
http://purl.uniprot.org/citations/23933573 | http://purl.uniprot.org/core/volume | "54"xsd:string |
http://purl.uniprot.org/citations/23933573 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23933573 |
http://purl.uniprot.org/citations/23933573 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23933573 |
http://purl.uniprot.org/uniprot/#_F2Z3U6-mappedCitation-23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/#_F6TSI8-mappedCitation-23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/#_P50172-mappedCitation-23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/#_Q4JHD9-mappedCitation-23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/#_Q3TJI8-mappedCitation-23933573 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/F6TSI8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/P50172 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/Q4JHD9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23933573 |
http://purl.uniprot.org/uniprot/Q3TJI8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23933573 |