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- Name help_outline 7-oxocholesterol Identifier CHEBI:64294 (Beilstein: 2169084; CAS: 566-28-9) help_outline Charge 0 Formula C27H44O2 InChIKeyhelp_outline YIKKMWSQVKJCOP-ABXCMAEBSA-N SMILEShelp_outline [H][C@@]1(CC[C@@]2([H])[C@]3([H])C(=O)C=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCCC(C)C 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,279 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 7β-hydroxycholesterol Identifier CHEBI:42989 (Beilstein: 3218479; CAS: 566-27-8) help_outline Charge 0 Formula C27H46O2 InChIKeyhelp_outline OYXZMSRRJOYLLO-KGZHIOMZSA-N SMILEShelp_outline [H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@@H](O)C=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCCC(C)C 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,285 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:68656 | RHEA:68657 | RHEA:68658 | RHEA:68659 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme.
Schweizer R.A.S., Zuercher M., Balazs Z., Dick B., Odermatt A.
The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the local activation of the glucocorticoid receptor by converting inactive 11-ketoglucocorticoids to active 11beta-hydroxyglucocorticoids is well established. Currently, 11beta-HSD1 is considered a promising target for treatme ... >> More
The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the local activation of the glucocorticoid receptor by converting inactive 11-ketoglucocorticoids to active 11beta-hydroxyglucocorticoids is well established. Currently, 11beta-HSD1 is considered a promising target for treatment of obese and diabetic patients. Here, we demonstrate a role of 11beta-HSD1 in the metabolism of 7-ketocholesterol (7KC), the major dietary oxysterol. Comparison of recombinant 11beta-HSD1, transiently expressed in human embryonic kidney 293 cells, revealed the stereo-specific interconversion of 7KC and 7beta-hydroxycholesterol by rat and human 11beta-HSD1, whereas the hamster enzyme interconverted 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, and 7KC. In contrast to lysates, which efficiently catalyzed both oxidation and reduction, intact cells exclusively reduced 7KC. These findings were confirmed using rat and hamster liver homogenates, intact rat hepatocytes, and intact hamster liver tissue slices. Reduction of 7KC was abolished upon inhibition of 11beta-HSD1 by carbenoxolone (CBX) or 2'-hydroxyflavanone. In vivo, after gavage feeding rats, 7KC rapidly appeared in the liver and was converted to 7beta-hydroxycholesterol. CBX significantly decreased the ratio of 7beta-hydroxycholesterol to 7KC, supporting the evidence from cell culture experiments for 11beta-HSD1-dependent reduction of 7KC to 7beta-hydroxycholesterol. Upon inhibition of 11beta-HSD1 by CBX, 7KC tended to accumulate in the liver, and plasma 7KC concentration increased. Together, our results suggest that 11beta-HSD1 efficiently catalyzes the first step in the rapid hepatic metabolism of dietary 7KC, which may explain why dietary 7KC has little or no effect on the development of atherosclerosis. << Less
J. Biol. Chem. 279:18415-18424(2004) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.
Hult M., Elleby B., Shafqat N., Svensson S., Rane A., Joernvall H., Abrahmsen L., Oppermann U.
Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyz ... >> More
Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7beta-hydroxycholesterol with similar k(cat) values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis. << Less