PathwayStep1594 PathwayStep1592 PathwayStep1593 PathwayStep1590 PathwayStep1591 PathwayStep1589 PathwayStep1588 PathwayStep1587 PathwayStep1586 PathwayStep1585 PathwayStep1583 PathwayStep1584 5beta-cholestan-3alpha,7alpha,27-triol is translocated from the cytosol to the mitochondrial matrix Efflux of 27-hydroxycholesterol Influx of 27-hydroxycholesterol 27-hydroxycholesterol is 7alpha-hydroxylated 5beta-cholestan-7alpha,27-diol-3-one is reduced to 5beta-cholestan-3alpha,7alpha,27-triol 5Beta-cholestan-7alpha,12alpha,27-triol-3-one is reduced to 5beta-cholestan-3alpha,7alpha,12alpha,27-tetrol 5beta-cholestan-3alpha,7alpha,12alpha,27-tetrol is translocated from the cytosol to the mitochondrial matrix 4-Cholesten-7alpha,27-diol-3-one is 12alpha-hydroxylated to 4-Cholesten-7alpha,12alpha,27-triol-3-one Cholest-5-ene-3beta,7alpha,27-triol + NAD+ => 4-cholesten-7alpha,27-diol-3-one +NADH + H+ 4-cholesten-7alpha,27-diol-3-one is reduced to 5beta-cholestan-7alpha,27-diol-3-one 4-cholesten-7alpha,12alpha,27-triol-3-one is reduced to 5beta-cholestan-7alpha,12alpha,27-triol-3-one Cholesterol is hydroxylated to 27-hydroxycholesterol by CYP27 Synthesis of bile acids and bile salts via 27-hydroxycholesterol Authored: D'Eustachio, P, 2007-02-27 21:49:11 Edited: D'Eustachio, P, 2007-02-27 21:49:11 GENE ONTOLOGYGO:0006699 In the body, 27-hydroxycholesterol is synthesized in multiple tissues, exported to the liver, and converted there to bile acids and bile salts. This pathway is only a minor source of bile acids and bile salts, but may play a significant role particularly in the mobilization of cholesterol from lung phagocytes (Bjorkhem et al. 1994; Babiker et al. 1999; Javitt 2002).<p>In the liver, conversion of 27-hydroxycholesterol to bile acids and bile salts is initiated with hydroxylation and oxidoreductase reactions to form 4-cholesten-7alpha,27-diol-3-one. The pathway then branches: hydroxylation of 4-cholesten-7alpha,27-diol-3-one to 4-cholesten-7alpha,12alpha,27-triol-3-one leads ultimately to the formation of cholate, while its reduction to 5beta-cholestan-7alpha,27-diol-3-one leads to chenodeoxycholate formation. In both branches, reactions in the cytosol, the mitochondrial matrix, and the peroxisomal matrix result in modifications to the ring structure, shortening and oxidation of the side chain, conversion to a Coenzyme A derivative, and conjugation with the amino acids glycine or taurine (Russell 2003). These reactions are outlined in the figure below. The final nine reactions are identical to ones of bile salt synthesis initiated by 7alpha-hydroxylation and are shown as arrows with no substrates. Pubmed10428977 Pubmed11969205 Pubmed12543708 Pubmed8078928 Reactome Database ID Release 43193807 Reactome, http://www.reactome.org ReactomeREACT_11048 Reviewed: D'Eustachio, P, 2007-04-30 14:43:26