Linked Life Data

10827156

Source:http://linkedlifedata.com/resource/pubmed/id/10827156

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-6-21
pubmed:abstractText
The biosynthesis of bile acids by primary cultures of normal human hepatocytes has been investigated. A general and sensitive method for the isolation and analysis of sterols and bile acids was used, based on anion exchange chromatography and gas chromatography-mass spectrometry (GC/MS). Following incubation for 5 days, 8 oxysterols and 8 C(27)- or C(24)-bile acids were identified in media and cells. Cholic and chenodeoxycholic acids conjugated with glycine or taurine were by far the major steroids found, accounting for 70% and 24% of the total, respectively, being consistent with bile acid synthesis in human liver. Small amounts of sulfated 3beta-hydroxy-5-cholenoic acid and 3beta,7alpha-dihydroxy-5beta-cholanoic acid were also detected. Nine steroids were potential bile acid precursors (2% of total), the major precursors being 7alpha, 12alpha-dihydroxy-3-oxo-4-cholenoic acid and its 5beta-reduced form. These 2 and 5 other intermediates formed a complete metabolic sequence from cholesterol to cholic acid (CA). This starts with 7alpha-hydroxylation of cholesterol, followed by oxidation to 7alpha-hydroxy-4-cholesten-3-one and 12alpha-hydroxylation. Notably, 27-hydroxylation of the product 7alpha, 12alpha-dihydroxy-4-cholesten-3-one and further oxidation and cleavage of the side chain precede A-ring reduction. A-Ring reduction may also occur before side-chain cleavage, but after 27-hydroxylation, yielding 3alpha,7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid as an intermediate. The amounts of the intermediates increased in parallel to those of CA during 4 days of incubation. Suppressing 27-hydroxylation with cyclosporin A (CsA) resulted in a 10-fold accumulation of 7alpha, 12alpha-dihydroxy-4-cholesten-3-one and a decrease of the production of CA and its acidic precursors. These results suggest that the observed intermediates reflect an alternative biosynthetic pathway to CA, which may be quantitatively significant in the cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1305-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Bile acid synthesis in cultured human hepatocytes: support for an alternative biosynthetic pathway to cholic acid.
pubmed:affiliation
Department of Clinical Chemistry, Karolinska Hospital, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. magnus.axelson@lab.ks.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't