J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ruan, B.
Right arrow Articles by Schroepfer, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruan, B.
Right arrow Articles by Schroepfer, G. J., , Jr.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 42, 799-812, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Sterols in blood of normal and Smith-Lemli-Opitz subjects

Benfang Ruanb, William K. Wilsona, Jihai Panga, Nicolas Gersta, Frederick D. Pinkertona, James Tsaia, Richard I. Kelleyc, Frank G. Whitbyd, Dianna M. Milewicze, James Garbernf, and George J. Schroepfer, Jr.a,b
a Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005
b Department of Chemistry, Rice University, Houston, TX 77005
c Kennedy Krieger Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205
d Department of Biochemistry, University of Utah, Salt Lake City, UT 84132
e Department of Internal Medicine, University of Texas-Houston Medical School, Houston, TX 77030
f Department of Neurology, Wayne State University, Detroit, MI 48201

Correspondence to: William K. Wilson, To whom correspondence should be addressed., billw{at}rice.edu (E-mail)

Smith-Lemli-Opitz syndrome (SLOS) is a hereditary disorder in which a defective gene encoding 7-dehydrocholesterol reductase causes the accumulation of noncholesterol sterols, such as 7- and 8-dehydrocholesterol. Using rigorous analytical methods in conjunction with a large collection of authentic standards, we unequivocally identified numerous noncholesterol sterols in 6 normal and 17 SLOS blood samples. Plasma or erythrocytes were saponified under oxygen-free conditions, followed by multiple chromatographic separations. Individual sterols were identified and quantitated by high performance liquid chromatography (HPLC), Ag+-HPLC, gas chromatography (GC), GC-mass spectrometry, and nuclear magnetic resonance. As a percentage of total sterol content, the major C27 sterols observed in the SLOS blood samples were cholesterol (12;–98%), 7-dehydrocholesterol (0.4;–44%), 8-dehydrocholesterol (0.5;–22%), and cholesta-5,7,9(11)-trien-3ß-ol (0.02;–5%), whereas the normal blood samples contained <0.03% each of the three noncholesterol sterols. SLOS and normal blood contained similar amounts of lathosterol (0.05;–0.6%) and cholestanol (0.1;–0.4%) and ~0.003;–0.1% each of the {Delta}8, {Delta}8(14), {Delta}5,8(14), {Delta}5,24, {Delta}6,8, {Delta}6,8(14), and {Delta}7,24 sterols.

The results are consistent with the hypothesis that the {Delta}8(14) sterol is an intermediate of cholesterol synthesis and indicate the existence of undescribed aberrant pathways that may explain the formation of the {Delta}5,7,9(11) sterol. 19-Norcholesta-5,7,9-trien-3ß-ol was absent in both SLOS and normal blood, although it was routinely observed as a GC artifact in fractions containing 8-dehydrocholesterol. The overall findings advance the understanding of SLOS and provide a methodological model for studying other metabolic disorders of cholesterol synthesis. — Ruan, B., W. K. Wilson, J. Pang, N. Gerst, F. D. Pinkerton, J. Tsai, R. I. Kelley, F. G. Whitby, D. M. Milewicz, J. Garbern, and G. J. Schroepfer, Jr. Sterols in blood of normal and Smith-Lemli-Opitz subjects. J. Lipid Res. 2001. 42: 799;–812.

Supplementary key words: SLOS, noncholesterol sterols, cholesta-5,8-dien-3ß-ol, Ag+-HPLC, NMR, GC-MS


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
R. B. Kodner, R. E. Summons, A. Pearson, N. King, and A. H. Knoll
Sterols in a unicellular relative of the metazoans
PNAS, July 22, 2008; 105(29): 9897 - 9902.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. A. Wassif, K. E. Brownson, A. L. Sterner, A. Forlino, P. M. Zerfas, W. K. Wilson, M. F. Starost, and F. D. Porter
HEM dysplasia and ichthyosis are likely laminopathies and not due to 3{beta}-hydroxysterol {Delta}14-reductase deficiency
Hum. Mol. Genet., May 15, 2007; 16(10): 1176 - 1187.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
M. Oostendorp, U. F.H. Engelke, M. A.A.P. Willemsen, and R. A. Wevers
Diagnosing Inborn Errors of Lipid Metabolism with Proton Nuclear Magnetic Resonance Spectroscopy
Clin. Chem., July 1, 2006; 52(7): 1395 - 1405.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. S. Pappu, R. D. Steiner, S. L. Connor, D. P. Flavell, D. S. Lin, L. Hatcher, D. R. Illingworth, and W. E. Connor
Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion
J. Lipid Res., October 1, 2002; 43(10): 1661 - 1669.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.