Reaction participants Show >> << Hide
- 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 testosterone Identifier CHEBI:17347 (Beilstein: 1915399,3653705; CAS: 58-22-0) help_outline Charge 0 Formula C19H28O2 InChIKeyhelp_outline MUMGGOZAMZWBJJ-DYKIIFRCSA-N SMILEShelp_outline [H][C@@]12CCC3=CC(=O)CC[C@]3(C)[C@@]1([H])CC[C@]1(C)[C@@H](O)CC[C@@]21[H] 2D coordinates Mol file for the small molecule Search links Involved in 18 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 16β,17β-dihydroxyandrost-4-en-3-one Identifier CHEBI:83027 Charge 0 Formula C19H28O3 InChIKeyhelp_outline YMCWOAZGWMZGQT-KYQPOWKGSA-N SMILEShelp_outline C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@]34C)[C@@H]1C[C@H](O)[C@@H]2O 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:46304 | RHEA:46305 | RHEA:46306 | RHEA:46307 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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| Gene Ontology help_outline |
Publications
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Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
Mast N., Norcross R., Andersson U., Shou M., Nakayama K., Bjoerkhem I., Pikuleva I.A.
The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol. This reaction produces biologically active oxysterol, 24(S)-hydroxycholesterol, and is also the first step in enzymatic degradation of cholesterol in the brain. We report here that P450 46A1 can further m ... >> More
The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol. This reaction produces biologically active oxysterol, 24(S)-hydroxycholesterol, and is also the first step in enzymatic degradation of cholesterol in the brain. We report here that P450 46A1 can further metabolize 24(S)-hydroxycholesterol, giving 24,25- and 24,27-dihydroxycholesterols in both the cell cultures transfected with P450 46A1 cDNA and the in vitro reconstituted system with recombinant enzyme. In addition, P450 46A1 was able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone). Also, P450 46A1 was found to metabolize xenobiotics carrying out dextromethorphan O- and N-demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation. Thus, substrate specificities of P450 46A1 are not limited to cholesterol and include a number of structurally diverse compounds. Activities of P450 46A1 suggest that, in addition to the involvement in cholesterol homeostasis in the brain, this enzyme may participate in metabolism of neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system. << Less
Biochemistry 42:14284-14292(2003) [PubMed] [EuropePMC]
This publication is cited by 7 other entries.
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Anandamide oxidation by wild-type and polymorphically expressed CYP2B6 and CYP2D6.
Sridar C., Snider N.T., Hollenberg P.F.
Anandamide is an arachidonic acid-derived endogenous cannabinoid that regulates normal physiological functions and pathophysiological responses within the central nervous system and in the periphery. Several cytochrome P450 (P450) isoforms metabolize anandamide to form hydroxylated and epoxygenate ... >> More
Anandamide is an arachidonic acid-derived endogenous cannabinoid that regulates normal physiological functions and pathophysiological responses within the central nervous system and in the periphery. Several cytochrome P450 (P450) isoforms metabolize anandamide to form hydroxylated and epoxygenated products. Human CYP2B6 and CYP2D6, which are expressed heterogeneously throughout the brain, exhibit clinically significant polymorphisms and are regulated by external factors, such as alcohol and smoking. Oxidative metabolism of anandamide by these two P450s may have important functional consequences for endocannabinoid system signaling. In this study, we investigated the metabolism of anandamide by wild-type CYP2B6 (2B6.1) and CYP2D6 (2D6.1) and by their common polymorphic mutants 2B6.4, 2B6.6, 2B6.9, and 2D6.34. Major differences in anandamide metabolism by the two isoforms and their mutants were found in vitro with respect to the formation of 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 14,15-epoxyeicosatetraenoic acid ethanolamide (14,15-EET-EA). Pharmacological studies showed that both 20-HETE-EA and 14,15-EET-EA bind to the rat brain cannabinoid CB1 receptor with lower affinities relative to that of anandamide. In addition, both products are degraded more rapidly than anandamide in rat brain homogenates. Their degradation occurs via different mechanisms involving either fatty acid amide hydrolase (FAAH), the major anandamide-degrading enzyme, or epoxide hydrolase (EH). Thus, the current findings provide potential new insights into the actions of inhibitors FAAH and EH, which are being developed as novel therapeutic agents, as well as a better understanding of the interactions between the cytochrome P450 monooxygenases and the endocannabinoid system. << Less
Drug Metab. Dispos. 39:782-788(2011) [PubMed] [EuropePMC]
This publication is cited by 5 other entries.