Reaction participants Show >> << Hide
- Name help_outline cholestanol Identifier CHEBI:86570 (CAS: 80-97-7) help_outline Charge 0 Formula C27H48O InChIKeyhelp_outline QYIXCDOBOSTCEI-QCYZZNICSA-N SMILEShelp_outline CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
reduced [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11964
Reactive part
help_outline
- Name help_outline FMNH2 Identifier CHEBI:57618 (Beilstein: 6258176) help_outline Charge -2 Formula C17H21N4O9P InChIKeyhelp_outline YTNIXZGTHTVJBW-SCRDCRAPSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])([O-])=O)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 771 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (24S)-hydroxycholestanol Identifier CHEBI:137687 Charge 0 Formula C27H48O2 InChIKeyhelp_outline DGZVTDWQDGXMNS-WWWAIJEQSA-N SMILEShelp_outline C1[C@@]2([C@]3(CC[C@]4([C@]([C@@]3(CC[C@]2(C[C@H](C1)O)[H])[H])(CC[C@@]4([C@H](C)CC[C@@H](C(C)C)O)[H])[H])C)[H])C 2D coordinates Mol file for the small molecule Search links Involved in 1 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 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
oxidized [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11965
Reactive part
help_outline
- Name help_outline FMN Identifier CHEBI:58210 Charge -3 Formula C17H18N4O9P InChIKeyhelp_outline ANKZYBDXHMZBDK-SCRDCRAPSA-K SMILEShelp_outline C12=NC([N-]C(C1=NC=3C(N2C[C@@H]([C@@H]([C@@H](COP(=O)([O-])[O-])O)O)O)=CC(=C(C3)C)C)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 781 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:53808 | RHEA:53809 | RHEA:53810 | RHEA:53811 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum.
Mast N., Anderson K.W., Lin J.B., Li Y., Turko I.V., Tatsuoka C., Bjorkhem I., Pikuleva I.A.
Cytochrome P450 27A1 (CYP27A1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereospecific hydroxylation of different sterols. In humans, complete CYP27A1 deficiency leads to cerebrotendinous xanthomatosis or nodule formation in tendons and brain (preferen ... >> More
Cytochrome P450 27A1 (CYP27A1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereospecific hydroxylation of different sterols. In humans, complete CYP27A1 deficiency leads to cerebrotendinous xanthomatosis or nodule formation in tendons and brain (preferentially in the cerebellum) rich in cholesterol and cholestanol, the 5α-saturated analog of cholesterol. In <i>Cyp27a1</i><sup>-/-</sup> mice, xanthomas are not formed, despite a significant cholestanol increase in the brain and cerebellum. The mechanism behind cholestanol production has been clarified, yet little is known about its metabolism, except that CYP27A1 might metabolize cholestanol. It also is unclear why CYP27A1 deficiency results in preferential cholestanol accumulation in the cerebellum. We hypothesized that cholestanol might be metabolized by CYP46A1, the principal cholesterol 24-hydroxylase in the brain. We quantified sterols along with CYP27A1 and CYP46A1 in mouse models (<i>Cyp27a1</i><sup>-/-</sup>, <i>Cyp46a1</i><sup>-/-</sup>, <i>Cyp27a1</i><sup>-/-</sup><i>Cyp46a1</i><sup>-/-</sup>, and two wild type strains) and human brain specimens. <i>In vitro</i> experiments with purified P450s were conducted as well. We demonstrate that CYP46A1 is involved in cholestanol removal from the brain and that several factors contribute to the preferential increase in cholestanol in the cerebellum arising from CYP27A1 deficiency. These factors include (i) low cerebellar abundance of CYP46A1 and high cerebellar abundance of CYP27A1, the lack of which probably selectively increases the cerebellar cholestanol production; (ii) spatial separation in the cerebellum of cholesterol/cholestanol-metabolizing P450s from a pool of metabolically available cholestanol; and (iii) weak cerebellar regulation of cholesterol biosynthesis. We identified a new physiological role of CYP46A1, an important brain enzyme and cytochrome P450 that could be activated pharmacologically. << Less
J. Biol. Chem. 292:4913-4924(2017) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.