Linked Life Data

3396133

Source:http://linkedlifedata.com/resource/pubmed/id/3396133

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1988-8-26
pubmed:abstractText
5 alpha-Cholest-8(14)-en-3 beta-ol-15-one is a potent inhibitor of sterol biosynthesis in mammalian cells in culture and has significant hypocholesterolemic activity upon oral administration to rodents and non-human primates. The conversion of the 15-ketosterol to cholesterol upon incubation with the 10,000 x g supernatant fraction of rat liver homogenate preparations under aerobic conditions has been reported (D.J. Monger, E.J. Parish and G.J. Schroepfer, Jr. (1980) J. Biol. Chem. 255, 11122-11129). Presented herein are results of studies of the metabolism of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one obtained upon incubation with the microsomal, cytosolic and the 10,000 x g supernatant fractions of liver homogenates of female rats under a variety of conditions. The results of these studies indicated metabolism of the 15-ketosterol to materials with the chromatographic properties of fatty acid esters of the 15-ketosterol, fatty acid esters of C27-monohydroxysterols, a component similar to the 15-ketosterol (possibly an isomer of the delta 8(14)-15-ketosterol), and a polar component. Detailed studies of the C27-monohydroxysterols obtained from incubation of the 15-ketosterol under anaerobic conditions indicated the formation of labeled 5 alpha-cholesta-8,14-dien-3 beta-ol and 5 alpha-cholest-7-en-3 beta-ol which were characterized by their behavior on silicic acid column chromatography, by the behavior of their acetate derivatives on medium pressure liquid chromatography on alumina-AgNO3 columns, and by co-crystallization of the labeled sterols with authentic unlabeled standards. The identification of 5 alpha-cholesta-8,14-dien-3 beta-ol and 5 alpha-cholest-7-en-3 beta-ol as metabolites of the 15-ketesterol, coupled with previous studies of the metabolism of 5 alpha-cholesta-8,14-dien-3 beta-ol and of 5 alpha-cholest-8(14)-ene-3 beta, 15 alpha-diol and 5 alpha-cholest-8(14)-ene-3 beta, 15 beta-diol has permitted the formulation of a scheme for the overall metabolism of the 15-ketosterol to cholesterol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0009-3084
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-46
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Inhibitors of cholesterol biosynthesis. Further studies of the metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one in rat liver preparations.
pubmed:affiliation
Department of Biochemistry, Rice University, Houston, TX 77251.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't