PathwayStep1616 PathwayStep1615 PathwayStep1614 PathwayStep1613 PathwayStep1612 PathwayStep1611 PathwayStep1610 PathwayStep1609 Cholesterol is released into the inner mitochondrial membrane Cholesterol translocates to the inner mitochondrial membrane Oxidation of 22beta-hydroxycholesterol to 20alpha,22beta-hydroxycholesterol Oxidation of cholesterol 20alpha,22beta-hydroxycholesterol is cleaved by CYP11A1 to yield pregnenolone and isocaproaldehyde Translocation of isocaproaldehyde from the mitochondrial matrix to the cytosol Reduction of isocaproaldehyde to 4-methylpentan-1-ol Pregnenolone translocates from the mitochondrial matrix to the cytosol Pregnenolone biosynthesis Authored: Jassal, B, 2008-10-01 13:18:42 Edited: Jassal, B, 2007-04-20 21:09:56 GENE ONTOLOGYGO:0006700 Pubmed11181954 Pubmed15583024 Reactome Database ID Release 43196108 Reactome, http://www.reactome.org ReactomeREACT_11038 Reviewed: D'Eustachio, P, 2007-04-20 21:11:21 The first process in the synthesis of all steroid hormones is the synthesis of pregnenolone from cholesterol. In this process, cholesterol mobilized from cytosolic lipid droplets or from lysosomes is transported to mitochondria and becomes localized to the inner mitochondrial membrane. Cholesterol transport appears to be rate-limiting for steroid hormone synthesis and its regulation, at the step of StAR-mediated traversal of the mitochondrial membrane, plays a central role in determining the amounts and identities of steroid hormones made in the body. In the inner mitochondrial membrane, cholesterol is converted to pregnenolone in a sequence of three reactions, all catalyzed by CYP11A (side chain cleavage enzyme). Finally, pregnenolone re-enters the cytosol (Payne and Hales 2004; Stocco 2001).