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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1 Pt 1
|
| pubmed:dateCreated |
1994-7-29
|
| pubmed:abstractText |
We investigated hepatic cholesterol homeostasis in four homozygous sitosterolemic subjects from two unrelated families who showed enhanced absorption, diminished removal and increased tissue and plasma concentrations of sitosterol (24-ethyl cholesterol). Measurements of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activities were correlated with steady state messenger RNA levels and related to cholesterol 7 alpha-hydroxylase activities in the sitosterolemic homozygotes and nine controls. Similar determinations were made in rats infused intravenously with sitosterol so that hepatic and plasma sitosterol concentrations increased to about 10% of total sterols to resemble the human disease sitosterolemia. In the four sitosterolemic homozygotes, hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activities were markedly reduced (12% of normal), and steady state 3-hydroxy-3-methylglutaryl coenzyme A reductase messenger RNA levels barely detected. In contrast, hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activities and messenger RNA levels were not decreased in rats with similarly elevated hepatic sitosterol concentrations. However, hepatic cholesterol 7 alpha-hydroxylase activity was inhibited 30% in both the sitosterolemic homozygotes and rats with high liver sitosterol concentrations. Plasma cholesterol concentrations increased 120% in the sitosterol-infused rats and 29% in the untreated human homozygotes. These results demonstrate that high-tissue sitosterol concentrations do not inhibit hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activityor steady state messenger RNA levels and that they competitively block cholesterol 7 alpha-hydroxylase activity and raise plasma cholesterol levels. Thus the deficiency of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of sitosterolemic homozygotes is inherited and not due to the hepatic accumulation of sitosterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol 7-alpha-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sitosterols
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0270-9139
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
20
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
213-9
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8020891-Adolescent,
pubmed-meshheading:8020891-Adult,
pubmed-meshheading:8020891-Animals,
pubmed-meshheading:8020891-Bile,
pubmed-meshheading:8020891-Bile Acids and Salts,
pubmed-meshheading:8020891-Binding, Competitive,
pubmed-meshheading:8020891-Cholesterol,
pubmed-meshheading:8020891-Cholesterol 7-alpha-Hydroxylase,
pubmed-meshheading:8020891-Female,
pubmed-meshheading:8020891-Homozygote,
pubmed-meshheading:8020891-Humans,
pubmed-meshheading:8020891-Hydroxymethylglutaryl CoA Reductases,
pubmed-meshheading:8020891-Lipid Metabolism, Inborn Errors,
pubmed-meshheading:8020891-Liver,
pubmed-meshheading:8020891-Male,
pubmed-meshheading:8020891-RNA, Messenger,
pubmed-meshheading:8020891-Rats,
pubmed-meshheading:8020891-Rats, Sprague-Dawley,
pubmed-meshheading:8020891-Sitosterols
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
The effect of increased hepatic sitosterol on the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7 alpha-hydroxylase in the rat and sitosterolemic homozygotes.
|
| pubmed:affiliation |
Sammy Davis Jr. National Liver Institute, University of Medicine and Newark 07103.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|