Document Detail

Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid.
MedLine Citation:
PMID:  7410549     Owner:  NLM     Status:  MEDLINE    
Oxidation of side chain of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was studied in a patient with cerebrotendinous xanthomatosis (CTX) and in control subjects, using various subcellular fractions of liver homogenate and a method based on isotope dilution-mass spectrometry. In the control, 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was converted into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by the mitochondrial fraction, and into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,-25-tetrol by the microsomal fraction. In the CTX patient, liver mitochondria were completely devoid of 26-hydroxylase activity. The same mitochondrial fraction catalyzed 25-hydroxylation of vitamin D3. The microsomal fraction of liver of the subject with CTX contained more than 50-fold the normal amount of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol. The basic metabolid defect in CTX appears to be a lack of the mitochondrial 26-hydroxylase. The excretion in the bile of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 alpha,25-pentol observed in CTX patients may be secondary to the accumulation of the major substrate for the 26-hydroxylase, i. e., 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, and exposure of this substrate to the normally less active microsomal 25-and 24-hydroxylases. It is concluded that the major pathway in the biosynthesis of cholic acid in human liver involves a mitochondrial C27-steroid 26-hydroxylation.
H Oftebro; I Björkhem; S Skrede; A Schreiner; J I Pederson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  65     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1980 Jun 
Date Detail:
Created Date:  1980-11-25     Completed Date:  1980-11-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1418-30     Citation Subset:  AIM; IM    
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MeSH Terms
Cholic Acids / biosynthesis*
Microsomes, Liver / metabolism
Mitochondria, Liver / enzymology*
Steroid Hydroxylases / deficiency,  metabolism*
Xanthomatosis / enzymology*
Reg. No./Substance:
0/Cholestanols; 0/Cholic Acids; EC 1.14.-/Steroid Hydroxylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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