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