biostudies-literatureGriffiths WJSwedish Foundation for Strategic ResearchEuropean UnionKarolinska InstitutetHjärnfondenSwedish Research CouncilBiotechnology and Biological Sciences Research CouncilCancerfondenBeacon Convergence projectEuropean Regional Development Fund191-211https://www.ebi.ac.uk/biostudies/studies/S-EPMC6327153biostudies-literatureUnknown1864(2)Cytochrome P450 (CYP) 27A1 is a key enzyme in both the acidic and neutral pathways of bile acid biosynthesis accepting cholesterol and ring-hydroxylated sterols as substrates introducing a (25R)26-hydroxy and ultimately a (25R)26-acid group to the sterol side-chain. In human, mutations in the CYP27A1 gene are the cause of the autosomal recessive disease cerebrotendinous xanthomatosis (CTX). Surprisingly, Cyp27a1 knockout mice (Cyp27a1-/-) do not present a CTX phenotype despite generating a similar global pattern of sterols. Using liquid chromatography - mass spectrometry and exploiting a charge-tagging approach for oxysterol analysis we identified over 50 cholesterol metabolites and precursors in the brain and circulation of Cyp27a1-/- mice. Notably, we identified (25R)26,7α- and (25S)26,7Biochimica et biophysica acta. Molecular and cell biology of lipidsAdditional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma.PMC63271532011-3318FO2015:0202FO2017-005920182016-01526BB/I001735/12016/572VR2011-3116BB/L001942/1BB/N015932/1SB16-0065Theofilopoulos SKelly DEYutuc EParker JEMeljon AAbdel-Khalik JKelly SLGriffiths WJArenas EWang YCrick PJfalseAdditional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma.Cytochrome P450 (CYP) 27A1 is a key enzyme in both the acidic and neutral pathways of bile acid biosynthesis accepting cholesterol and ring-hydroxylated sterols as substrates introducing a (25R)26-hydroxy and ultimately a (25R)26-acid group to the sterol side-chain. In human, mutations in the CYP27A1 gene are the cause of the autosomal recessive disease cerebrotendinous xanthomatosis (CTX). Surprisingly, Cyp27a1 knockout mice (Cyp27a1-/-) do not present a CTX phenotype despite generating a similar global pattern of sterols. Using liquid chromatography - mass spectrometry and exploiting a charge-tagging approach for oxysterol analysis we identified over 50 cholesterol metabolites and precursors in the brain and circulation of Cyp27a1-/- mice. Notably, we identified (25R)26,7α- and (25S)26,72019-01-01T00:00:00Z2019 Feb2025-04-22T07:31:32.321Z2019-03-26T22:47:32ZS-EPMC63271533047142510.1016/j.bbalip.2018.11.006