Document Detail

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.
MedLine Citation:
PMID:  6848555     Owner:  NLM     Status:  MEDLINE    
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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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  71     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1983 Jan 
Date Detail:
Created Date:  1983-02-25     Completed Date:  1983-02-25     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:  142-8     Citation Subset:  AIM; IM    
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MeSH Terms
Bile Acids and Salts / biosynthesis*
Chenodeoxycholic Acid / biosynthesis
Lipid Metabolism, Inborn Errors / enzymology*
Liver / enzymology
Steroid Hydroxylases / deficiency*
Reg. No./Substance:
0/Bile Acids and Salts; 474-25-9/Chenodeoxycholic Acid; EC 1.14.-/Steroid Hydroxylases

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

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