Free radical oxidation of cholesterol and its precursors: Implications in cholesterol biosynthesis disorders

References

• Shrivastava S, Paila YD, Dutta A, Chattopadhyay A. Differential effects of cholesterol and its immediate biosynthetic precursors on membrane organization. Biochemistry 2008;47:5668–5677.
   PubMedGoogle Scholar
• Rog T, Vattulainen I, Jansen M, Ikonen E, Karttunen M. Comparison of cholesterol and its direct precursors along the biosynthetic pathway: effects of cholesterol, desmosterol and 7-dehydrocholesterol on saturated and unsaturated lipid bilayers. J Chem Phys 2008;129:154508.
   PubMedGoogle Scholar
• Brown DA, London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 1998;14:111–136.
   PubMed Web of Science ®Google Scholar
• Korade Z, Kenworthy AK. Lipid rafts, cholesterol, and the brain. Neuropharmacology 2008;55:1265–1273.
   PubMed Web of Science ®Google Scholar
• Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signaling proteins in animal development. Science 1996;274:255–259.
   PubMed Web of Science ®Google Scholar
• Cooper MK, Wassif CA, Krakowiak PA, Taipale J, Gong R, Kelley RI, et al. A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis. Nat Genet 2003;33:508–513.
   PubMed Web of Science ®Google Scholar
• Jurevics H, Morell P. Cholesterol for synthesis of myelin is made locally, not imported into brain. J Neurochem 1995;64:895–901.
   PubMed Web of Science ®Google Scholar
• Brown AJ, Jessup W. Oxysterols and atherosclerosis. Atherosclerosis 1999;142:1–28.
   PubMed Web of Science ®Google Scholar
• Vaya J, Schipper HM. Oxysterols, cholesterol homeostasis, and Alzheimer disease. J Neurochem 2007;102:1727–1737.
   PubMed Web of Science ®Google Scholar
• Rodriguez IR, Fliesler SJ. Photodamage generates 7-keto- and 7-hydroxycholesterol in the rat retina via a free radical-mediated mechanism. Photochem Photobiol 2009;85:1116–1125.
   PubMedGoogle Scholar
• Rodriguez IR, Larrayoz IM. Cholesterol oxidation in the retina: Implications of 7KCh formation in chronic inflammation and age-related macular degeneration. J Lipid Res 2010;51:2847–2862.
   PubMed Web of Science ®Google Scholar
• Girao H, Mota MC, Ramalho J, Pereira P. Cholesterol oxides accumulate in human cataracts. Exp Eye Res 1998;66: 645–652.
   PubMed Web of Science ®Google Scholar
• Vejux A, Samadi M, Lizard G. Contribution of cholesterol and oxysterols in the physiopathology of cataract: Implication for the development of pharmacological treatments. J Ophthalmol 2011;2011:471947.
   PubMedGoogle Scholar
• Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V, Gale SE, et al. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med 2010;2:56ra81.
   Google Scholar
• Xu L, Davis TA, Porter NA. Rate constants for peroxidation of polyunsaturated fatty acids and sterols in solution and in liposomes. J Am Chem Soc 2009;131:13037–13044.
   PubMed Web of Science ®Google Scholar
• Xu L, Porter NA. Reactivities and products of free radical oxidation of cholestadienols. J Am Chem Soc 2014;136: 5443–5450.
   PubMedGoogle Scholar
• Xu L, Korade Z, Porter NA. Oxysterols from free radical chain oxidation of 7-dehydrocholesterol: Product and mechanistic studies. J Am Chem Soc 2010;132:2222–2232.
   PubMed Web of Science ®Google Scholar
• Korade Z, Xu L, Shelton R, Porter NA. Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome. J Lipid Res 2010;51: 3259–3269.
   PubMedGoogle Scholar
• Xu L, Korade Z, Rosado DA, Liu W, Lamberson CR, Porter NA. An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome. J Lipid Res 2011;52:1222–1233.
   PubMed Web of Science ®Google Scholar
• Xu L, Liu W, Sheflin LG, Fliesler SJ, Porter NA. Novel oxysterols observed in tissues and fluids of AY9944-treated rats – a model for Smith-Lemli-Opitz Syndrome. J Lipid Res 2011;52:1810–1820.
   PubMed Web of Science ®Google Scholar
• Xu L, Mirnics K, Bowman AB, Liu W, Da J, Porter NA, Korade Z. DHCEO accumulation is a critical mediator of pathophysiology in a Smith-Lemli-Opitz syndrome model. Neurobiol Dis 2012;45:923–929.
   PubMed Web of Science ®Google Scholar
• Korade Z, Xu L, Mirnics K, Porter NA. Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome. J Inherit Metab Dis 2013;36:113–122.
   PubMedGoogle Scholar
• Xu L, Korade Z, Rosado DA Jr, Mirnics K, Porter NA. Metabolism of oxysterols derived from nonenzymatic oxidation of 7-dehydrocholesterol in cells. J Lipid Res 2013;54:1135–1143.
   PubMed Web of Science ®Google Scholar
• Korade Z, Xu L, Harrison FE, Ahsen R, Hart SE, Folkes OM, et al. Antioxidant supplementation ameliorates molecular deficits in Smith-Lemli-Opitz syndrome. Biol Psychiatry 2014;75:215–222.
   PubMedGoogle Scholar
• Smith LL. Cholesterol autoxidation 1981–1986. Chem Phys Lipids 1987;44:87–125.
   PubMed Web of Science ®Google Scholar
• Sevilla C, Becker D, Sevilla M. An electron spin resonance investigation of radical intermediates in cholesterol and related compounds: relation to solid-state autoxidation. J Phys Chem 1986;90:2963–2968.
   Google Scholar
• Chisolm GM, Ma G, Irwin KC, Martin LL, Gunderson KG, Linberg LF et al. 7 beta-hydroperoxycholest-5-en-3 beta-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein. Proc Natl Acad Sci U S A 1994;91:11452–11456.
   PubMed Web of Science ®Google Scholar
• Brown AJ, Leong SL, Dean RT, Jessup W. 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. J Lipid Res 1997;38:1730–1745.
   PubMed Web of Science ®Google Scholar
• Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res 2010;51: 3299–3305.
   PubMed Web of Science ®Google Scholar
• Smith LL, Johnson BH. Biological activities of oxysterols. Free Radic Biol Med 1989;7:285–332.
   PubMed Web of Science ®Google Scholar
• Schroepfer GJ Jr. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 2000;80:361–554.
   PubMed Web of Science ®Google Scholar
• Javitt NB. Oxysteroids: a new class of steroids with autocrine and paracrine functions. Trends Endocrinol Metab 2004;15:393–397.
   PubMedGoogle Scholar
• Javitt NB. Oxysterols: novel biologic roles for the 21st century. Steroids 2008;73:149–157.
   PubMed Web of Science ®Google Scholar
• Porter FD, Herman GE. Malformation syndromes caused by disorders of cholesterol synthesis. J Lipid Res 2011;52: 6–34.
   PubMed Web of Science ®Google Scholar
• Irons M, Elias ER, Salen G, Tint GS, Batta AK. Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome. Lancet 1993;341:1414.
   PubMed Web of Science ®Google Scholar
• Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, Salen G. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994;330: 107–113.
   PubMed Web of Science ®Google Scholar
• Tint GS, Seller M, Hughes-Benzie R, Batta AK, Shefer S, Genest D, et al. Markedly increased tissue concentrations of 7-dehydrocholesterol combined with low levels of cholesterol are characteristic of the Smith-Lemli-Opitz syndrome. J Lipid Res 1995;36:89–95.
   PubMed Web of Science ®Google Scholar
• Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet 2000;37:321–335.
   PubMedGoogle Scholar
• Krakowiak PA, Nwokoro NA, Wassif CA, Battaile KP, Nowaczyk MJ, Connor WE, et al. Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping. Am J Med Genet 2000;94:214–227.
   PubMed Web of Science ®Google Scholar
• Honda A, Tint GS, Salen G, Batta AK, Chen TS, Shefer S. Defective conversion of 7-dehydrocholesterol to cholesterol in cultured skin fibroblasts from Smith-Lemli-Opitz syndrome homozygotes. J Lipid Res 1995;36:1595–1601.
   PubMed Web of Science ®Google Scholar
• Kandutsch AA, Russell AE. Preputial gland tumor sterols. 3. A metabolic pathway from lanosterol to cholesterol. J Biol Chem 1960;235:2256–2261.
   PubMed Web of Science ®Google Scholar
• Bloch K. Sterol molecule: structure, biosynthesis, and function. Steroids 1992;57:378–383.
   PubMed Web of Science ®Google Scholar
• Holick MF, Frommer JE, McNeill SC, Richtand NM, Henley JW, Potts JT Jr. Photometabolism of 7-dehydrocholesterol to previtamin D3 in skin. Biochem Biophys Res Commun 1977;76:107–114.
   PubMed Web of Science ®Google Scholar
• Windsor K, Genaro-Mattos TC, Kim HY, Liu W, Tallman KA, Miyamoto S, et al. Probing lipid-protein adduction with alkynyl surrogates: application to Smith-Lemli-Opitz syndrome. J Lipid Res 2013;54:2842–2850.
   PubMed Web of Science ®Google Scholar
• Bjorkhem I, Diczfalusy U. Oxysterols: friends, foes, or just fellow passengers? Arterioscler. Thromb Vasc Biol 2002;22:734–742.
   PubMed Web of Science ®Google Scholar
• Vejux A, Lizard G. Cytotoxic effects of oxysterols associated with human diseases: induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med 2009;30:153–170.
   PubMed Web of Science ®Google Scholar
• Brown AJ, Jessup W. Oxysterols: sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol Aspects Med 2009;30:111–122.
   PubMed Web of Science ®Google Scholar
• Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev 2011;111:5944–5972.
   PubMed Web of Science ®Google Scholar
• Iuliano L. Pathways of cholesterol oxidation via non-enzymatic mechanisms. Chem Phys Lipids 2011;164:457–468.
   PubMed Web of Science ®Google Scholar
• Howard JA, Ingold JA. Absolute rate constants for hydrocarbon autoxidation .6. Alkyl aromatic and olefinic hydrocarbons. Can J Chem 1967;45:793–802.
   Web of Science ®Google Scholar
• Trenwith AB. Dissociation of 3-methylpenta-1, 4-diene and the resonance energy of the pentadienyl radical. J Chem Soc Faraday Trans I 1982;78:3131–3136.
   Google Scholar
• Berkowitz J, Ellison GB, Gutman D. Three methods to measure RH bond energies. J Phys Chem 1994;98:2744–2765.
   Web of Science ®Google Scholar
• Pratt DA, Mills JH, Porter NA. Theoretical calculations of carbon-oxygen bond dissociation enthalpies of peroxyl radicals formed in the autoxidation of lipids. J Am Chem Soc 2003;125:5801–5810.
   PubMed Web of Science ®Google Scholar
• Roschek B Jr, Tallman KA, Rector CL, Gillmore JG, Pratt DA, Punta C, Porter NA. Peroxyl radical clocks. J Org Chem 2006;71:3527–3532.
   PubMedGoogle Scholar
• Carreira LA. Determination of the torsional potential function of 1,3-butadiene. J Chem Phys 1975;62:3851–3854.
   Google Scholar
• Giese B. Formation of CC bonds by addition of free radicals to alkenes. Angew Chem Int Ed 1983;22:753–764.
   Google Scholar
• Porter NA, Mills KA, Carter RL. A mechanistic study of oleate autoxidation: competing peroxyl H-atom abstraction and rearrangement. J Am Chem Soc 1994;116:6690–6696.
   Web of Science ®Google Scholar
• Tallman KA, Pratt DA, Porter NA. Kinetic products of linoleate peroxidation: Rapid beta-fragmentation of nonconjugated peroxyls. J Am Chem Soc 2001;123:11827–11828.
   PubMedGoogle Scholar
• Tallman KA, Roschek B Jr, Porter NA. Factors influencing the autoxidation of fatty acids: effect of olefin geometry of the nonconjugated diene. J Am Chem Soc 2004;126: 9240–9247.
   PubMedGoogle Scholar
• Brash AR. Autoxidation of methyl linoleate: identification of the bis-allylic 11-hydroperoxide. Lipids 2000;35:947–952.
   PubMed Web of Science ®Google Scholar
• Beckwith ALJ, Davies AG, Davison IGE, Maccoll A, Mruzek MH. The mechanisms of the rearrangements of allylic hydroperoxides: 5-alpha-hydroperoxy-3-beta-hydroxycholest-6-ene and 7-alpha-hydroperoxy-3-beta-hydroxycholest-5-ene. J Chem Soc Perkin Trans 2 1989;7:815–824.
   Google Scholar
• Porter NA, Funk M. Peroxy radical cyclization as a model for prostaglandin biosynthesis. J Org Chem 1975;40: 3614–3615.
   PubMed Web of Science ®Google Scholar
• Porter NA, Funk MO, Gilmore DW, Isaac R, Nixon J. The formation of cyclic peroxides from unsaturated hydroperoxides: Models for prostaglandin biosynthesis. J Am Chem Soc 1976;98:6000–6005.
   PubMedGoogle Scholar
• Porter NA, Lehman LS, Weber BA, Smith KJ. Unified mechanism for polyunsaturated fatty acid autoxidation. Competition of peroxy radical hydrogen atom abstraction, .beta.-scission, and cyclization . J Am Chem Soc 1981;103: 6447–6455.
   Web of Science ®Google Scholar
• Morrow JD, Awad JA, Boss HJ, Blair IA, Roberts LJ II. Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. Proc Natl Acad Sci U S A 1992;89:10721–10725.
   PubMed Web of Science ®Google Scholar
• Milne GL, Yin H, Hardy KD, Davies SS, Roberts LJ. Isoprostane generation and function. Chem Rev 2011; 111:5973–5996.
   PubMed Web of Science ®Google Scholar
• Roberts LJ II, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 1998;273:13605–13612.
   PubMed Web of Science ®Google Scholar
• Russell GA. Deuterium-isotope effects in the autoxidation of aralkyl hydrocarbons. mechanism of the interaction of PEroxy radicals. J Am Chem Soc 1957;79:3871–3877.
   Web of Science ®Google Scholar
• Howard J, Ingold K. Self-reaction of sec-butylperoxy radicals. Confirmation of the Russell mechanism. J Am Chem Soc 1968;90:1056–1058.
   Web of Science ®Google Scholar
• Dix TA, Marnett LJ. Conversion of linoleic acid hydroperoxide to hydroxy, keto, epoxyhydroxy, and trihydroxy fatty acids by hematin. J Biol Chem 1985;260:5351–5357.
   PubMed Web of Science ®Google Scholar
• Bowry VW, Stocker R. Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc 1993;115:6029–6044.
   Google Scholar
• Ingold KU, Bowry VW, Stocker R, Walling C. Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein. Proc Natl Acad Sci U S A 1993;90:45–49.
   PubMed Web of Science ®Google Scholar
• Lamberson CR, Xu L, Muchalski H, Montenegro-Burke JR, Shmanai VV, Bekish AV, et al. Unusual kinetic isotope effects of deuterium reinforced polyunsaturated fatty acids in tocopherol-mediated free radical chain oxidations. J Am Chem Soc 2014;136:838–841.
   PubMedGoogle Scholar
• Kulig MJ, Smith LL. Sterol metabolism. XXV. Cholesterol oxidation by singlet molecular oxygen. J Org Chem 1973;38:3639–3642.
   Google Scholar
• Girotti AW. Photosensitized oxidation of cholesterol in biological systems: reaction pathways, cytotoxic effects and defense mechanisms. J Photochem Photobiol B 1992;13:105–118.
   PubMed Web of Science ®Google Scholar
• Albro PW, Corbett JT, Schroeder JL. Doubly allylic hydroperoxide formed in the reaction between sterol 5,7-dienes and singlet oxygen. Photochem Photobiol 1994;60:310–315.
   PubMedGoogle Scholar
• Albro PW, Bilski P, Corbett JT, Schroeder JL, Chignell CF. Photochemical reactions and phototoxicity of sterols: Novel self-perpetuating mechanism for lipid photooxidation. Photochem Photobiol 1997;66:316–325.
   PubMed Web of Science ®Google Scholar
• Pulfer MK, Murphy RC. Formation of biologically active oxysterols during ozonolysis of cholesterol present in lung surfactant. J Biol Chem 2004;279:26331–26338.
   PubMed Web of Science ®Google Scholar
• Pulfer MK, Taube C, Gelfand E, Murphy RC. Ozone exposure in vivo and formation of biologically active oxysterols in the lung. J Pharmacol Exp Ther 2005;312:256–264.
   PubMed Web of Science ®Google Scholar
• Gumulka J, Smith LL. Ozonation of cholesterol. J Am Chem Soc 1983;105:1972–1979.
   Web of Science ®Google Scholar
• Jaworski K, Smith LL. Ozonization of cholesterol in nonparticipating solvents. J Org Chem 1988;53:545–554.
   Web of Science ®Google Scholar
• Wang K, Bermudez E, Pryor WA. The ozonation of cholesterol: separation and identification of 2,4-dinitrophenylhydrazine derivatization products of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al. Steroids 1993;58:225–229.
   PubMedGoogle Scholar
• Zhang Q, Powers ET, Nieva J, Huff ME, Dendle MA, Bieschke J, et al. Metabolite-initiated protein misfolding may trigger Alzheimer's disease. Proc Natl Acad Sci U S A 2004;101:4752–4757.
   PubMed Web of Science ®Google Scholar
• Nieva J, Song BD, Rogel JK, Kujawara D, Altobel L III, Izharrudin A, et al. Cholesterol secosterol aldehydes induce amyloidogenesis and dysfunction of wild-type tumor protein p53. Chem Biol 2011;18:920–927.
   PubMedGoogle Scholar
• Brinkhorst J, Nara SJ, Pratt DA. Hock cleavage of cholesterol 5alpha-hydroperoxide: An ozone-free pathway to the cholesterol ozonolysis products identified in arterial plaque and brain tissue. J Am Chem Soc 2008;130:12224–12225.
   PubMed Web of Science ®Google Scholar
• Shinkyo R, Xu L, Tallman KA, Cheng Q, Porter NA, Guengerich FP. Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate. J Biol Chem 2011;286:33021–33028.
   PubMed Web of Science ®Google Scholar
• Xu L, Sheflin LG, Porter NA, Fliesler SJ. 7-Dehydrocholesterol-derived oxysterols and retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Biochim Biophys Acta 2012;1821:877–883.
   PubMed Web of Science ®Google Scholar
• Liu W, Xu L, Lamberson CR, Merkens LS, Steiner RD, Elias ER, et al. Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients. J Lipid Res 2013;54:244–253.
   PubMedGoogle Scholar
• Goyal S, Xiao Y, Porter NA, Xu L, Guengerich FP. Oxidation of 7-Dehydrocholesterol and Desmosterol by Human Cytochrome P450 46A1. J Lipid Res 2014;55:1933–1943.
   PubMed Web of Science ®Google Scholar
• Charman CR, Ryan A, Tyrrell RM, Pearse AD, Arlett CF, Kurwa HA, et al. Photosensitivity associated with the Smith-Lemli-Opitz syndrome. Br J Dermatol 1998;138:885–888.
   PubMedGoogle Scholar
• Sikora D, Pettit-Kekel K, Penfield J, Merkens L, Steiner R. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet 2006;140A:1511–1518.
   Google Scholar
• Weenen H, Porter NA. Autoxidation of model membrane systems: Cooxidation of polyunsaturated lecithins with steroids, fatty acids, and alpha-tocopherol. J Am Chem Soc 1982;104:5216–5221.
   Google Scholar
• De Fabiani E, Caruso D, Cavaleri M, Galli Kienle M, Galli G. Cholesta-5,7,9(11)-trien-3 beta-ol found in plasma of patients with Smith-Lemli-Opitz syndrome indicates formation of sterol hydroperoxide. J Lipid Res 1996;37: 2280–2287.
   PubMedGoogle Scholar
• Vaughan DK, Peachey NS, Richards MJ, Buchan B, Fliesler SJ. Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Exp Eye Res 2006;82:496–504.
   PubMedGoogle Scholar
• Richards MJ, Nagel BA, Fliesler SJ. Lipid hydroperoxide formation in the retina: correlation with retinal degeneration and light damage in a rat model of Smith-Lemli-Opitz syndrome. Exp Eye Res 2006;82:538–541.
   PubMedGoogle Scholar
• Valencia A, Kochevar IE. Ultraviolet A induces apoptosis via reactive oxygen species in a model for Smith-Lemli-Opitz syndrome. Free Radic Biol Med 2006;40:641–650.
   PubMed Web of Science ®Google Scholar
• Valencia A, Rajadurai A, Carle AB, Kochevar IE. 7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: Roles of NADPH oxidase, mitochondria, and lipid rafts. Free Radic Biol Med 2006; 41:1704–1718.
   PubMedGoogle Scholar
• Gaoua W, Chevy F, Roux C, Wolf C. Oxidized derivatives of 7-dehydrocholesterol induce growth retardation in cultured rat embryos: a model for antenatal growth retardation in the Smith-Lemli-Opitz syndrome. J Lipid Res 1999;40: 456–463.
   PubMedGoogle Scholar
• Schneider C, Tallman KA, Porter NA, Brash AR. Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of non-enzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals. J Biol Chem 2001;276:20831–20838.
   PubMed Web of Science ®Google Scholar
• Schopfer FJ, Cipollina C, Freeman BA. Formation and signaling actions of electrophilic lipids. Chem Rev 2011;111:5997–6021.
   PubMed Web of Science ®Google Scholar
• Kelley RI. Diagnosis of Smith-Lemli-Opitz syndrome by gas chromatography/mass spectrometry of 7-dehydrocholesterol in plasma, amniotic fluid and cultured skin fibroblasts. Clin Chim Acta 1995;236:45–58.
   PubMedGoogle Scholar
• Haas D, Garbade SF, Vohwinkel C, Muschol N, Trefz FK, Penzien JM, et al. Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). J Inherit Metab Dis 2007;30:375–387.
   PubMedGoogle Scholar