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24-Hydroxycholester...
24-Hydroxycholesterol is a substrate for hepatic cholesterol 7 alpha-hydroxylase (CYP7A)
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- Norlin, Maria (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharm Biochemistry
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- Toll, Anders (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharm Biochemistry
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- Bjorkhem, Ingemar (författare)
- Karolinska Institutet
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- Wikvall, Kjell (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharm Biochemistry
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(creator_code:org_t)
- 2000
- 2000
- Engelska.
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 41:10, s. 1629-1639
- Relaterad länk:
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- (24S)-Hydroxycholesterol is formed from cholesterol in the brain and is important for cholesterol homeostasis in this organ. Elimination of (24S)-hydroxycholesterol has been suggested to occur in the liver but little is known about the metabolism of this oxysterol. In the present investigation, we report formation of 7alpha, 24-dihydroxycholesterol in pig and human liver. 7alpha-hydroxylase activity toward both isomers of 24-hydroxycholesterol [(24S) and (24R)] was found in a partially purified and reconstituted cholesterol 7alpha-hydroxylase (CYP7A) enzyme fraction from pig liver microsomes. In contrast, a purified enzyme fraction of pig liver oxysterol 7alpha-hydroxylase with high activity toward 27-hydroxycholesterol did not show any detectable activity toward 24-hydroxycholesterol. 7alpha-Hydroxylation of 24-hydroxycholesterol was strongly inhibited by 7-oxocholesterol, a known inhibitor of CYP7A. Human CYP7A, recombinantly expressed in Escherichia coli and in simian COS cells, showed 7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol, with a preference for the (24S)-isomer. Our results show that 24-hydroxycholesterol is metabolized by CYP7A, an enzyme previously considered to be specific for cholesterol and cholestanol and not active toward oxysterols. Because CYP7A is the rate-limiting enzyme in the major pathway of bile acid biosynthesis, the possibility is discussed that at least part of the 24-hydroxycholesterol is converted into 7alpha-hydroxylated bile acids by the enzymes involved in the normal biosynthesis of bile acids.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- hepatic metabolism
- oxysterols
- cholesterol
- cytochrome P-450
- bile acid biosynthesis
- PHARMACY
- FARMACI
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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