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http://purl.uniprot.org/citations/18065749http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18065749http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18065749http://www.w3.org/2000/01/rdf-schema#comment"Long-chain 3-hydroxydicarboxylic acids (3-OHDCAs) are thought to arise via beta-oxidation of the corresponding dicarboxylic acids (DCAs), although long-chain DCAs are neither readily transported into nor beta-oxidized in mitochondria. We thus examined whether omega-hydroxylation of 3-hydroxy fatty acids (3-OHFAs), formed via incomplete mitochondrial oxidation, is a more likely pathway for 3-OHDCA production. NADPH-fortified human liver microsomes converted 3-hydroxystearate and 3-hydroxypalmitate to their omega-hydroxylated metabolites, 3,18-dihydroxystearate and 3,16-dihydroxypalmitate, respectively, as identified by GC-MS. Rates of 3,18-dihydroxystearate and 3,16-dihydroxypalmitate formation were 1.23 +/- 0.5 and 1.46 +/-0.30 nmol product formed/min/mg protein, respectively (mean +/-SD; n = 13). Polyspecific CYP4F antibodies markedly inhibited microsomal omega-hydroxylation of 3-hydroxystearate (68%) and 3-hydroxypalmitate (99%), whereas CYP4A11 and CYP2E1 antibodies had little effect. Upon reconstitution, CYP4F11 and, to a lesser extent, CYP4F2 catalyzed omega-hydroxylation of 3-hydroxystearate, whereas CYP4F3b, CYP4F12, and CYP4A11 exhibited negligible activity. CYP4F11 was the lone CYP4F/A enzyme that effectively oxidized 3-hydroxypalmitate. Kinetic parameters of microsomal 3-hydroxystearate metabolism were K(m) = 55 microM and V(max) = 8.33 min(-1), whereas those for 3-hydroxypalmitate were K(m) = 56.4 microM and V(max) = 14.2 min(-1). CYP4F11 kinetic values resembled those of native microsomes, with K(m) = 53.5 microM and V(max) = 13.9 min(-1) for 3-hydroxystearate and K(m) = 105.8 microM and V(max) = 70.6 min(-1) for 3-hydroxypalmitate. Our data show that 3-hydroxystearate and 3-hydroxypalmitate are converted to omega-hydroxylated 3-OHDCA precursors in human liver and that CYP4F11 is the predominant catalyst of this reaction. CYP4F11-promoted omega-hydroxylation of 3-OHFAs may modulate the disposition of these compounds in pathological states in which enhanced fatty acid mobilization or impairment of mitochondrial fatty acid beta-oxidation increases circulating 3-OHFA levels."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.org/dc/terms/identifier"doi:10.1194/jlr.m700450-jlr200"xsd:string
http://purl.uniprot.org/citations/18065749http://purl.org/dc/terms/identifier"doi:10.1194/jlr.m700450-jlr200"xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Dhar M."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Dhar M."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Hirani V."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Hirani V."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Lasker J.M."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Lasker J.M."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Magnusson R.P."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Magnusson R.P."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Sepkovic D.W."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/author"Sepkovic D.W."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/name"J. Lipid Res."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/name"J. Lipid Res."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/pages"612-624"xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/pages"612-624"xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/title"Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/title"Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11."xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/volume"49"xsd:string
http://purl.uniprot.org/citations/18065749http://purl.uniprot.org/core/volume"49"xsd:string
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