Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1

Journal of Lipid Research

Volumn 55, Issue 9, 2014, Pages 1933-1943

  Goyal, Sandeep ^a   Xiao, Yi ^a   Porter, Ned A ^a   Xu, Libin ^a   Guengerich, F Peter ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

24 Hydroxy 7 dehydrocholesterol; 24S,25 epoxycholesterol; 25 Hydroxy 7 dehydrocholesterol; 27 Hydroxydesmosterol

Indexed keywords

7 DEHYDROCHOLESTEROL; 7-DEHYDROCHOLESTEROL; CHOLESTEROL 24-HYDROXYLASE; DESMOSTEROL; PROTEIN BINDING; STEROID MONOOXYGENASE;

CHEMISTRY; HUMAN; KINETICS; OXIDATION REDUCTION REACTION;

DEHYDROCHOLESTEROLS; DESMOSTEROL; HUMANS; KINETICS; OXIDATION-REDUCTION; PROTEIN BINDING; STEROID HYDROXYLASES;

EID: 84906874549     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M051508     Document Type: Article

References (54)

1. Mast, N., R. Norcross, U. Andersson, M. Shou, K. Nakayama, I. Björkhem, and I. A. Pikuleva. 2003. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 42: 14284-14292.
2. Pikuleva, I. A. 2006. Cholesterol-metabolizing cytochromes P450. Drug Metab. Dispos. 34: 513-520.
3. Janowski, B. A., P. J. Willy, T. R. Devi, J. R. Falck, and D. J. Mangelsdorf. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 383: 728-731.
4. Janowski, B. A., M. J. Grogan, S. A. Jones, G. B. Wisely, S. A. Kliewer, E. J. Corey, and D. J. Mangelsdorf. 1999. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA. 96: 266-271.
5. Radhakrishnan, A., Y. Ikeda, H. J. Kwon, M. S. Brown, and J. L. Goldstein. 2007. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc. Natl. Acad. Sci. USA. 104: 6511-6518.
6. Holick, M. F., J. E. Frommer, S. C. McNeill, N. M. Richtand, J. W. Henley, and J. T. Potts, Jr. 1977. Photometabolism of 7-dehydrocholesterol to previtamin D3 in skin. Biochem. Biophys. Res. Commun. 76: 107-114.
7. Porter, F. D., and G. E. Herman. 2011. Malformation syndromes caused by disorders of cholesterol synthesis. J. Lipid Res. 52: 6-34.
8. Kelley, R. I., and R. C. Hennekam. 2000. The Smith-Lemli-Opitz syndrome. J. Med. Genet. 37: 321-335.
9. de Sain-van der Velden, M. G., A. Verrips, B. H. Prinsen, M. de Barse, R. Berger, and G. Visser. 2008. Elevated cholesterol precursors other than cholestanol can also be a hallmark for CTX. J. Inherit. Metab. Dis. 31(Suppl 2): S387-S393.
10. Tint, G. S., M. Irons, E. R. Elias, A. K. Batta, R. Frieden, T. S. Chen, and G. Salen. 1994. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N. Engl. J. Med. 330: 107-113.
11. Witsch-Baumgartner, M., B. U. Fitzky, M. Ogorelkova, H. G. Kraft, F. F. Moebius, H. Glossmann, U. Seedorf, G. Gillessen-Kaesbach, G. F. Hoffmann, P. Clayton, et al. 2000. Mutational spectrum in the delta 7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome. Am. J. Hum. Genet. 66: 402-412.
12. Xu, L., W. Liu, L. G. Sheflin, S. J. Fliesler, and N. A. Porter. 2011. Novel oxysterols observed in tissues and fluids of AY9944-treated rats - a model for Smith-Lemli-Opitz syndrome. J. Lipid Res. 52: 1810-1820.
13. Björkhem, I., L. Starck, U. Andersson, D. Lutjohann, S. von Bahr, I. Pikuleva, A. Babiker, and U. Diczfalusy. 2001. Oxysterols in the circulation of patients with the Smith-Lemli-Opitz syndrome: abnormal levels of 24S- and 27-hydroxycholesterol. J. Lipid Res. 42: 366-371.
14. Xu, L., T. A. Davis, and N. A. Porter. 2009. Rate constants for peroxidation of polyunsaturated fatty acids and sterols in solution and in liposomes. J. Am. Chem. Soc. 131: 13037-13044.
15. Xu, L., Z. Korade, and N. A. Porter. 2010. Oxysterols from free radical chain oxidation of 7-dehydrocholesterol: product and mechanistic studies. J. Am. Chem. Soc. 132: 2222-2232.
16. Korade, Z., L. Xu, R. Shelton, and N. A. Porter. 2010. Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome. J. Lipid Res. 51: 3259-3269.
17. Xu, L., Z. Korade, D. A. Rosado, W. Liu, C. R. Lamberson, and N. A. Porter. 2011. An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome. J. Lipid Res. 52: 1222-1233.
18. Xu, L., Z. Korade, D. A. Rosado, Jr., K. Mirnics, and N. A. Porter. 2013. Metabolism of oxysterols derived from nonenzymatic oxidation of 7-dehydrocholesterol in cells. J. Lipid Res. 54: 1135-1143.
19. Xu, L., and N. A. Porter. 2014. Reactivities and products of free radical oxidation of cholestadienols. J. Am. Chem. Soc. 136: 5443-5450.
20. Shinkyo, R., L. Xu, K. A. Tallman, Q. Cheng, N. A. Porter, and F. P. Guengerich. 2011. 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. 286: 33021-33028.
21. Björkhem, I., U. Diczfalusy, A. Lovgren-Sandblom, L. Starck, M. Jonsson, K. Tallman, H. Schirmer, L. Bomme Ousager, P. J. Crick, Y. Wang, et al. 2014. On the formation of 7-ketocholesterol from 7-dehydrocholesterol in patients with CTX and SLO. J. Lipid Res. 55: 1165-1172.
22. Muchmore, D. C., L. P. McIntosh, C. B. Russell, D. E. Anderson, and F. W. Dahlquist. 1989. Expression and nitrogen-15 labeling of proteins for proton and nitrogen-15 nuclear magnetic resonance. Methods Enzymol. 177: 44-73.
23. Barnes, H. J., M. P. Arlotto, and M. R. Waterman. 1991. Expression and enzymatic activity of recombinant cytochrome P450 17α-hydroxylase in Escherichia coli. Proc. Natl. Acad. Sci. USA. 88: 5597-5601.
24. Barnes, H. J. 1996. Maximizing expression of eukaryotic cytochrome P450s in Escherichia coli. Methods Enzymol. 272: 3-14.
25. Sandhu, P., T. Baba, and F. P. Guengerich. 1993. Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, purification, and reconstitution of catalytic activity. Arch. Biochem. Biophys. 306: 443-450.
26. Omura, T., and R. Sato. 1964. The carbon monoxide-binding pigment of liver microsomes. I. evidence for its hemoprotein nature. J. Biol. Chem. 239: 2370-2378.
27. Hanna, I. H., J. F. Teiber, K. L. Kokones, and P. F. Hollenberg. 1998. Role of the alanine at position 363 of cytochrome P450 2B2 in influencing the NADPH- and hydroperoxide-supported activities. Arch. Biochem. Biophys. 350: 324-332.
28. Guengerich, F. P., and C. J. Bartleson. 2007. Analysis and characterization of enzymes and nucleic acids. In Principles and Methods of Toxicology. A. W. Hayes, editor. CRC Press, Boca Raton, FL. 1981-2048.
29. Kuzmic, P. 1996. Program DYNAFIT for the analysis of enzyme kinetic data: application to HIV proteinase. Anal. Biochem. 237: 260-273.
30. Shinkyo, R., and F. P. Guengerich. 2011. Cytochrome P450 7A1 cholesterol 7α-hydroxylation: individual reaction steps in the catalytic cycle and rate-limiting ferric iron reduction. J. Biol. Chem. 286: 4632-4643.
31. Mast, N., and I. A. Pikuleva. 2005. A simple and rapid method to measure cholesterol binding to P450s and other proteins. J. Lipid Res. 46: 1561-1568.
32. Björkhem, I., D. Lutjohann, U. Diczfalusy, L. Stahle, G. Ahlborg, and J. Wahren. 1998. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J. Lipid Res. 39: 1594-1600.
33. McDonald, J. G., B. M. Thompson, E. C. McCrum, and D. W. Russell. 2007. Extraction and analysis of sterols in biological matrices by high performance liquid chromatography electrospray ionization mass spectrometry. Methods Enzymol. 432: 145-170.
34. Karu, K., M. Hornshaw, G. Woffendin, K. Bodin, M. Hamberg, G. Alvelius, J. Sjovall, J. Turton, Y. Wang, and W. J. Griffiths. 2007. Liquid chromatography-mass spectrometry utilizing multi-stage fragmentation for the identification of oxysterols. J. Lipid Res. 48: 976-987.
35. Griffiths, W. J., and Y. Wang. 2009. Analysis of neurosterols by GC-MS and LC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877: 2778-2805.
36. Lütjohann, D., O. Breuer, G. Ahlborg, I. Nennesmo, A. Sidén, U. Diczfalusy, and I. Björkhem. 1996. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc. Natl. Acad. Sci. USA. 93: 9799-9804.
37. Bretillon, L., A. Sidén, L. O. Wahlund, D. Lütjohann, L. Minthon, M. Crisby, J. Hillert, C. G. Groth, U. Diczfalusy, and I. Björkhem. 2000. Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci. Lett. 293: 87-90.
38. Korade, Z., L. Xu, K. Mirnics, and N. A. Porter. 2013. Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome. J. Inherit. Metab. Dis. 36: 113-122.
39. Endo-Umeda, K., K. Yasuda, K. Sugita, A. Honda, M. Ohta, M. Ishikawa, Y. Hashimoto, T. Sakaki, and M. Makishima. 2014. 7-Dehydrocholesterol metabolites produced by sterol 27-hydroxylase (CYP27A1) modulate liver X receptor activity. J. Steroid Biochem. Mol. Biol. 140: 7-16.
40. Wassif, C. A., J. Yu, J. Cui, F. D. Porter, and N. B. Javitt. 2003. 27-Hydroxylation of 7- and 8-dehydrocholesterol in Smith-Lemli-Opitz syndrome: a novel metabolic pathway. Steroids. 68: 497-502.
41. Shackleton, C., E. Roitman, L. W. Guo, W. K. Wilson, and F. D. Porter. 2002. Identification of 7(8) and 8(9) unsaturated adrenal steroid metabolites produced by patients with 7-dehydrosterol-delta7-reductase deficiency (Smith-Lemli-Opitz syndrome). J. Steroid Biochem. Mol. Biol. 82: 225-232.
42. Marcos, J., L. W. Guo, W. K. Wilson, F. D. Porter, and C. Shackleton. 2004. The implications of 7-dehydrosterol-7-reductase deficiency (Smith-Lemli-Opitz syndrome) to neurosteroid production. Steroids. 69: 51-60.
43. Nelson, J. A., S. R. Steckbeck, and T. A. Spencer. 1981. Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide. J. Biol. Chem. 256: 1067-1068.
44. Meljon, A., S. Theofilopoulos, C. H. Shackleton, G. L. Watson, N. B. Javitt, H. J. Knolker, R. Saini, E. Arenas, Y. Wang, and W. J. Griffiths. 2012. Analysis of bioactive oxysterols in newborn mouse brain by LC/MS. J. Lipid Res. 53: 2469-2483.
45. Theofilopoulos, S., Y. Wang, S. S. Kitambi, P. Sacchetti, K. M. Sousa, K. Bodin, J. Kirk, C. Salto, M. Gustafsson, E. M. Toledo, et al. 2013. Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nat. Chem. Biol. 9: 126-133.
46. Dennick, R. G., P. D. Dean, and D. A. Abramovich. 1973. Desmosterol levels in human foetal brain - a reassessment. J. Neurochem. 20: 1293-1294.
47. Fumagalli, R., and R. Paoletti. 1963. The identification and significance of desmosterol in the developing human and animal brain. Life Sci. 5: 291-295.
48. Quan, G., C. Xie, J. M. Dietschy, and S. D. Turley. 2003. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res. Dev. Brain Res. 146: 87-98.
49. Lütjohann, D., A. Brzezinka, E. Barth, D. Abramowski, M. Staufenbiel, K. von Bergmann, K. Beyreuther, G. Multhaup, and T. A. Bayer. 2002. Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J. Lipid Res. 43: 1078-1085.
50. Meljon, A., Y. Wang, and W. J. Griffiths. 2014. Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse. Biochem. Biophys. Res. Commun. 446: 768-774.
51. Zerenturk, E. J., I. Kristiana, S. Gill, and A. J. Brown. 2012. The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1). Biochim. Biophys. Acta. 1821: 1269-1277.
52. Mast, N., C. Charvet, I. A. Pikuleva, and C. D. Stout. 2010. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain. J. Biol. Chem. 285: 31783-31795.
53. Mast, N., Y. Li, M. Linger, M. Clark, J. Wiseman, and I. A. Pikuleva. 2014. Pharmacologic stimulation of cytochrome P450 46A1 and cerebral cholesterol turnover in mice. J. Biol. Chem. 289: 3529-3538.
54. Clayton, P., K. Mills, J. Keeling, and D. FitzPatrick. 1996. Desmosterolosis: a new inborn error of cholesterol biosynthesis. Lancet. 348: 404.