Source:http://linkedlifedata.com/resource/pubmed/id/12077124
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
35
|
| pubmed:dateCreated |
2002-8-30
|
| pubmed:abstractText |
One of the major oxysterols in the human circulation is 4 beta-hydroxycholesterol formed from cholesterol by the drug-metabolizing enzyme cytochrome P450 3A4. Deuterium-labeled 4 beta-hydroxycholesterol was injected into two healthy volunteers, and the apparent half-life was found to be 64 and 60 h, respectively. We have determined earlier the half-lives for 7 alpha-, 27-, and 24-hydroxycholesterol to be approximately 0.5, 0.75, and 14 h, respectively. Patients treated with certain antiepileptic drugs have up to 20-fold increased plasma concentrations of 4 beta-hydroxycholesterol. The apparent half-life of deuterium-labeled 4 beta-hydroxycholesterol in such a patient was found to be 52 h, suggesting that the high plasma concentration was because of increased synthesis rather than impaired clearance. 4 beta-Hydroxycholesterol was converted into acidic products at a much slower rate than 7 alpha-hydroxycholesterol in primary human hepatocytes, and 4 beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1. CYP7B1 and CYP39A1 had no activity toward 4 beta-hydroxycholesterol. These results suggest that the high plasma concentration of 4 beta-hydroxycholesterol is because of its exceptionally slow elimination, probably in part because of the low rate of 7 alpha-hydroxylation of the steroid. The findings are discussed in relation to a potential role of 4 beta-hydroxycholesterol as a ligand for the nuclear receptor LXR.
|
| 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/CYP3A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP3A,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxycholesterols,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/cholest-5-ene-3,4-diol
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
30
|
| pubmed:volume |
277
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
31534-40
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:12077124-Bile Acids and Salts,
pubmed-meshheading:12077124-Cell Line,
pubmed-meshheading:12077124-Cells, Cultured,
pubmed-meshheading:12077124-Cytochrome P-450 CYP3A,
pubmed-meshheading:12077124-Cytochrome P-450 Enzyme System,
pubmed-meshheading:12077124-Female,
pubmed-meshheading:12077124-Half-Life,
pubmed-meshheading:12077124-Hepatocytes,
pubmed-meshheading:12077124-Humans,
pubmed-meshheading:12077124-Hydroxycholesterols,
pubmed-meshheading:12077124-Infusions, Intravenous,
pubmed-meshheading:12077124-Kidney,
pubmed-meshheading:12077124-Kinetics,
pubmed-meshheading:12077124-Male,
pubmed-meshheading:12077124-Mass Spectrometry,
pubmed-meshheading:12077124-Metabolic Clearance Rate,
pubmed-meshheading:12077124-Mixed Function Oxygenases,
pubmed-meshheading:12077124-Recombinant Proteins
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Metabolism of 4 beta -hydroxycholesterol in humans.
|
| pubmed:affiliation |
Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|