4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol is reduced to 4,4-dimethylcholesta-8(9),24-dien-3beta-ol [LBR] 4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol + NADPH + H+ => 4,4-dimethylcholesta-8(9),24-dien-3beta-ol + NADP+ [LBR] 4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol and NADPH + H+ react to form 4,4-dimethylcholesta-8(9),24-dien-3beta-ol and NADP+, catalyzed by LBR in the nuclear envelope. LBR protein spans the inner nuclear envelope, has an aminoterminal region with properties of a laminin receptor and a carboxyterminal domain with sequence similarity to sterol delta14-reductases (Holmer et al. 1998). Studies of material from an individual with HEM/Greenberg skeletal dysplasia indicate that LBR catalyzes the sterol delta14-reductase step of cholesterol biosynthesis in vivo. DNA sequencing revealed homozygosity for a mutant LBR allele encoding a truncated protein in the affected individual, and cells from the individual accumulated cholesta-8,14-dien-3beta-ol in culture. Transfection of wild-type LBR into the cultured cells reversed the accumulation of cholesta-8,14-dien-3beta-ol (Waterham et al. 2003). This observation is surprising because a second gene, TM7SF2, encodes an efficient sterol delta14-reductase that is localized to the endoplasmic reticulum whose expression is up-regulated in response to sterol depletion (Bennati et al. 2006). The physiological roles of LBR and TM7SF2 in vivo remain to be determined. Authored: D'Eustachio, P, 2007-04-21 18:31:40 EC Number: 1.3.1.70 Edited: D'Eustachio, P, 2007-04-21 18:31:40 Pubmed12618959 Pubmed16784888 Pubmed9878250 Reactome Database ID Release 43194674 Reactome, http://www.reactome.org ReactomeREACT_9995 Reviewed: Jassal, B, 2007-04-21 18:33:24