Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.
I Björkhem, … , J I Pedersen, S Skrede
I Björkhem, … , J I Pedersen, S Skrede
Published January 1, 1983
Citation Information: J Clin Invest. 1983;71(1):142-148. https://doi.org/10.1172/JCI110742.
View: Text | PDF
Research Article

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.

  • Text
  • PDF
Abstract

On the basis of different in vitro studies, we have previously suggested that the basic metabolic defect in the rare inherited disease cerebrotendinous xanthomatosis (CTX) is a lack of a hepatic mitochondrial C27-steroid 26-hydroxylase, involved in the normal biosynthesis of bile acids (1980. J. Clin. Invest. 65: 1418-1430; 1981. J. Lipid Res. 22: 191-200; 22: 632-640). In the present work, this hypothesis was tested in vivo. One patient with CTX and two control subjects received intravenously a mixture of [4-14C]7 alpha-hydroxy-4-cholesten-3-one and [6 beta-3H]7 alpha,26-dihydroxy-4-cholesten-3-one, steroids believed to be important precursors of chenodeoxycholic acid. The ratio between 14C and 3H in cholic acid and chenodeoxycholic acid isolated from bile of the CTX-patient was approximately 1/40 and 1/60 of those of the control subjects, respectively. Another patient with CTX and one control subject received a mixture of [4-14C]5 beta-cholestane-3 alpha,7 alpha-diol and [1,2-3H]5 beta-cholestane-3 alpha,7 alpha,26-triol, both possible precursors to chenodeoxycholic acid. In this case the 14C/3H ratio in cholic acid and chenodeoxycholic acid from the patient with CTX was 1/10 and 1/15, respectively, compared with that of the control subject. The most likely explanation for these findings is that very little of the 14C-precursors, i.e. without a 26-hydroxyl group, can be converted into cholic acid and chenodeoxycholic acid because of a defect of the 26-hydroxylase step. The results obtained are in accord with our previous findings in vitro. The results further underline the importance of the 26-hydroxylase pathway in the normal biosynthesis of cholic acid and chenodeoxycholic acid in man.

Authors

I Björkhem, O Fausa, G Hopen, H Oftebro, J I Pedersen, S Skrede

×

Total citations by year

Year: 2023 2019 2018 2012 2011 2010 2008 2005 2003 2000 1999 1997 1996 1995 1994 1993 1992 1991 1990 1988 1987 1986 1985 1984 1983 Total
Citations: 1 1 1 2 1 1 2 2 1 1 1 2 2 1 3 3 1 6 2 5 4 3 7 2 4 59
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (59)

Title and authors Publication Year
Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia
Chun MY, Heo NJ, Seo SW, Jang H, Suh YL, Jang JH, Kim YE, Kim EJ, Moon SY, Jung NY, Lee SM, Kim HJ
Frontiers in neurology 2023
Adult Leukodystrophies: A Step-by-Step Diagnostic Approach
LL Resende, AR de Paiva, F Kok, C da Costa Leite, LT Lucato
Radiographics 2019
Adulthood leukodystrophies
W Köhler, J Curiel, A Vanderver
Nature Reviews Neurology 2018
Genetic and metabolic liver disease
RJ Thompson, BC Portmann, EA Roberts
MacSween s Pathology of the Liver 2012
MacSween's Pathology of the Liver
RJ Thompson, BC Portmann, EA Roberts
MacSween's Pathology of the Liver 2012
Advances in Clinical Chemistry
M Mahler
Advances in Clinical Chemistry Volume 54 2011
Cerebrotendinous xanthomatosis: An inborn error in bile acid synthesis with defined mutations but still a challenge
I Björkhem, M Hansson
Biochemical and Biophysical Research Communications 2010
Cerebrotendinous xanthomatosis: a critical update
LF Gonzalez-Cuyar, AL Morrison, G Perry, JJ DeJong, MA Smith, RJ Castellani
Future Neurology 2008
Studies in Natural Products Chemistry
M Seki
Studies in Natural Products Chemistry 2008
Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype
L Guyant-Maréchal, A Verrips, C Girard, RA Wevers, F Zijlstra, E Sistermans, P Vera, D Campion, D Hannequin
American Journal of Medical Genetics Part A 2005
Cytochrome P450
PR de Montellano
Cytochrome P450 2005
Genetics of Movement Disorders
E Bertini, C Dionisi-Vici, M Zeviani
Genetics of Movement Disorders 2003
Smith-Lemli-Opitz syndrome and other sterol disorders among Finns with developmental disabilities
MJ Nissinen, H Gylling, M Kaski, P Tammisto, S Mieskonen, J Ignatius, TA Miettinen
Journal of Laboratory and Clinical Medicine 2000
Anomalous enantioselectivity in the sharpless asymmetric dihydroxylation reaction of 24-nor-5β-cholest-23-ene-3α,7α,12α-triol: Synthesis of substrates for studies of cholesterol side-chain oxidation
NH Ertel, B Dayal, K Rao, G Salen
Lipids 1999
7β-hydroxy bile alcohols: Facile synthesis and 2D 1H NMR studies of 5β-cholestane-3α,7β,12α,25-tetrol
B Dayal, NH Ertel, J Padia, KR Rapole, G Salen
Steroids 1997
Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families
W Chen, S Kubota, KS Kim, J Cheng, M Kuriyama, G Eggertsen, I Björkhem, Y Seyama
Journal of lipid research 1997
Genetic analysis of a Japanese cerebrotendinous xanthomatosis family: identification of a novel mutation in the adrenodoxin binding region of the CYP 27 gene
W Chen, S Kubota, Y Nishimura, S Nozaki, S Yamashita, T Nakagawa, K Kameda-Takemura, M Menju, Y Matsuzawa, I Björkhem, G Eggertsen, Y Seyama
Biochimica et Biophysica Acta 1996
Relationship between the Serum Concentration of 7α-Hydroxycholesterol and Fecal Bile Acid Excretion in Humans
C Hahn, K Bergmann
Scandinavian Journal of Gastroenterology 1996
Magnetic resonance imaging of cerebrotendinous xanthomatosis
KS Tai, J Brockwell, FL Chan, ED Janus, KS Lam
Australasian Radiology 1995
Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages
I Björkhem, O Andersson, U Diczfalusy, B Sevastik, RJ Xiu, C Duan, E Lund
Proceedings of the National Academy of Sciences 1994
Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use
M Kuriyama, Y Tokimura, J Fujiyama, Y Utatsu, M Osame
Journal of the Neurological Sciences 1994
A point mutation in the bile acid biosynthetic enzyme sterol 27-hydroxylase in a family with cerebrotendinous xanthomatosis
N Nakashima, Y Sakai, H Sakai, T Yanase, M Haji, F Umeda, S Koga, T Hoshita, H Nawata
Journal of lipid research 1994
Peroxisomal oxidation of the steroid side chain in bile acid formation
JI Pedersen
Biochimie 1993
Bile alcohol glucuronides: regioselective O-glucuronidation of 5β-cholestane-3α,7α,12α,25-tetrol and 24-nor-5β-cholestane-3α,7α,12α,25-tetrol
B Dayal, G Salen, J Padia, S Shefer, GS Tint, G Sasso, TH Williams
Carbohydrate Research 1993
Synthesis of 27-hydroxycholesterol in rat liver mitochondria: HPLC assay and marked activation by exogenous cholesterol
B Petrack, BJ Latario
Journal of lipid research 1993
Mechanism of degradation of the steroid side chain in the formation of bile acids
I Björkhem
Journal of lipid research 1992
Combined treatment with chenodeoxycholic acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis
T Nakamura, Y Matsuzawa, K Takemura, M Kubo, H Miki, S Tarui
Metabolism 1991
Metabolic aspects of peroxisomal β-oxidation
H Osmundsen, J Bremer, JI Pedersen
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1991
Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis
J J Cali, C L Hsieh, U Francke, D W Russell
The Journal of biological chemistry 1991
Mutations in the Bile Acid Biosynthetic Enzyme Sterol 27-Hydroxylase Underlie Cerebrotendinous Xanthomatosis*
James J. Cali, Chih-Lin Hsieh, Uta Francke, David W. Russell
The Journal of biological chemistry 1991
Metabolic Basis of Cholesterol Gallstone Disease
AD Cooper
Gastroenterology Clinics of North America 1991
Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis
JJ Cali, DW Russell
The Journal of biological chemistry 1991
Effect of Bile Alcohols on the Microbial 7α-dehydroxylation of Chenodeoxycholic acid
A Lindqvist, T Midtvedt, S Skrede, J Sjövall
Microbial Ecology in Health and Disease 1990
Use of positive ion fast atom bombardment mass spectrometry for rapid identification of a bile alcohol glucuronide isolated from cerebrotendinous xanthomatosis patients
B Dayal, G Salen, GS Tint, S Shefer, SW Benz
Steroids 1990
Plasma and biliary cholestanol related to steroid metabolism in familial hypercholesterolemia patients with and without ileal exclusion
PV Koivisto, TA Miettinen
Clinica Chimica Acta 1988
Reduced C 27 -steroid 26-hydroxylase activity in heterozygotes for cerebrotendinous xanthomatosis
S Skrede, I Björkhem, EA Kvittingen, C East, S Grundy, S Skrede
Scandinavian Journal of Clinical & Laboratory Investigation 1988
The Bile Acids: Chemistry, Physiology, and Metabolism
KD Setchell, D Kritchevsky, PP Nair
1988
Hepatic 7 alpha-dehydroxylation of bile acid intermediates, and its significance for the pathogenesis of cerebrotendinous xanthomatosis
S Skrede, MS Buchmann, I Björkhem
Journal of lipid research 1988
Cerebrotendinous xanthomatosis: A review of biochemical findings of the patient population in the netherlands
BJ Koopman, BG Wolthers, JC van der Molen, W van der Slik, RJ Waterreus, A van Spreeken
Journal of Inherited Metabolic Disease 1988
Accumulation of 7α-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in patients with cerebrotendinous xanthomatosis: Effect of treatment with chenodeoxycholic acid
I Björkhem, S Skrede, MS Buchmann, C East, S Grundy
Hepatology 1987
Cerebrotendinous xanthomatosis (CTX): A clinical survey of the patient population in the Netherlands
RJ Waterreus, BJ Koopman, BG Wolthers, HJ Oosterhuis
Clinical Neurology and Neurosurgery 1987
Metabolism of the cholestanol precursor cholesta-4,6-dien-3-one in different tissues
MS Buchmann, I Björkhem, S Skrede
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1987
Peroxisomes in Biology and Medicine
HD Fahimi, H Sies
1987
Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in cerebrotendinous xanthomatosis
S Skrede, I Björkhem, EA Kvittingen, MS Buchmann, SO Lie, C East, S Grundy
Journal of Clinical Investigation 1986
Effects of cholestanol feeding and cholestyramine treatment on the tissue sterols in the rabbit
MS Buchmann, OP Clausen
Lipids 1986
Increased (23R)-hydroxylase activity in patients suffering from cerebrotendinous xanthomatosis, resulting in (23R)-hydroxylation of bile acids
BJ Koopman, BG Wolthers, JC der Molen, GT Nagel, H Rutgers, B Strijtveen, B Kaptein
Biochimica et Biophysica Acta (BBA) - General Subjects 1986
Defective peroxisomal cleavage of the C27-steroid side chain in the cerebro-hepato-renal syndrome of Zellweger
BF Kase, I Björkhem, P Hågå, JI Pedersen
Journal of Clinical Investigation 1985
A novel pathway for biosynthesis of cholestanol with 7 alpha-hydroxylated C27-steroids as intermediates, and its importance for the accumulation of cholestanol in cerebrotendinous xanthomatosis
S Skrede, I Björkhem, MS Buchmann, G Hopen, O Fausa
Journal of Clinical Investigation 1985
Biosynthesis of bile acids in cerebrotendinous xanthomatosis. Relationship of bile acid pool sizes and synthesis rates to hydroxylations at C-12, C-25, and C-26
G Salen, S Shefer, GS Tint, G Nicolau, B Dayal, AK Batta
Journal of Clinical Investigation 1985
Bile acid therapies applied to patients suffering from cerebrotendinous xanthomatosis
BJ Koopman, BG Wolthers, JC der Molen, RJ Waterreus
Clinica Chimica Acta 1985
Studies of the Mechanism of the Increased Biosynthesis of Cholestanol in Cerebrotendinous Xanthomatosis: The Activity of Δ 5 -3β-Hydroxysteroid Dehydrogenase
MS Buchmann, I Björkhem, O Fausa, S Skrede
Scandinavian Journal of Gastroenterology 1985
Biosynthesis of cholestanol from bile acid intermediates in the rabbit and the rat
S Skrede, I Björkhem, MS Buchmann, T Midtvedt
The Journal of biological chemistry 1985
Identification of bile alcohols in human bile
S Kuroki, K Shimazu, M Kuwabara, M Une, K Kihira, T Kuramoto, T Hoshita
Journal of lipid research 1985
Capillary gas chromatographic determination of cholestanol/cholesterol ratio in biological fluids. Its potential usefulness for the follow-up of some liver diseases and its lack of specificity in diagnosing CTX (cerebrotendinous xanthomatosis)
BJ Koopman, JC der Molen, BG Wolthers, AE Jager, RJ Waterreus, CH Gips
Clinica Chimica Acta 1984
Capillary gas chromatographic determinations of urinary bile acids and bile alcohols in CTX patients proving the ineffectivity of ursodeoxycholic acid treatment
BJ Koopman, BG Wolthers, JC der Molen, GT Nagel, RJ Waterreus, HJ Oosterhuis
Clinica Chimica Acta 1984
Identification of 5 β-cholestane-3 α, 7 α, 12 α, 25, 26-pentol in cerebrotendinous xanthomatosis
B Dayal, GS Tint, DN Greeley, TH Williams, G Salen
Steroids 1983
New Comprehensive Biochemistry
S Yamamoto
New Comprehensive Biochemistry 1983
Isolation of 5α-cholestane-3β,7α-diol from bile of patients with cerebrotendinous xanthomatosis
I Björkhem, MS Buchmann, S Skrede
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1983
Evidence for a lack of regulatory importance of the 12 alpha-hydroxylase in formation of bile acids in man: an in vivo study
I Björkhem, M Eriksson, K Einarsson
Journal of lipid research 1983

← Previous 1 2 3 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts