Enzymes
UniProtKB help_outline | 2 proteins |
Reaction participants Show >> << Hide
- Name help_outline all-trans-retinoate Identifier CHEBI:35291 Charge -1 Formula C20H27O2 InChIKeyhelp_outline SHGAZHPCJJPHSC-YCNIQYBTSA-M SMILEShelp_outline CC(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(C)=C/C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 8 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 all-trans-5,6-epoxyretinoate Identifier CHEBI:139183 Charge -1 Formula C20H27O3 InChIKeyhelp_outline KEEHJLBAOLGBJZ-WEDZBJJJSA-M SMILEShelp_outline C12(C(CCCC1(C)O2)(C)C)/C=C/C(=C/C=C/C(=C/C([O-])=O)/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 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:55860 | RHEA:55861 | RHEA:55862 | RHEA:55863 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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Publications
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Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases.
Smith G., Wolf C.R., Deeni Y.Y., Dawe R.S., Evans A.T., Comrie M.M., Ferguson J., Ibbotson S.H.
<h4>Background</h4>Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handli ... >> More
<h4>Background</h4>Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies.<h4>Methods</h4>We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis.<h4>Findings</h4>We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme.<h4>Interpretation</h4>These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis. << Less
Lancet 361:1336-1343(2003) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites.
Marill J., Cresteil T., Lanotte M., Chabot G.G.
Cytochrome P450 (P450)-dependent metabolism of all-trans-retinoic acid (atRA) is important for the expression of its biological activity. Because the human P450s involved in the formation of the principal atRA metabolites have been only partially identified, the purpose of this study was to identi ... >> More
Cytochrome P450 (P450)-dependent metabolism of all-trans-retinoic acid (atRA) is important for the expression of its biological activity. Because the human P450s involved in the formation of the principal atRA metabolites have been only partially identified, the purpose of this study was to identify the human P450s involved in atRA metabolism. The use of phenotyped human liver microsomes (n = 16) allowed the identification of the following P450s: 2B6, 2C8, 3A4/5, and 2A6 were involved in the formation of 4-OH-RA and 4-oxo-RA; 2B6, 2C8, and 2A6 correlated with the formation of 18-OH-RA; and 2A6, 2B6, and 3A4/5 activities correlated with 5, 6-epoxy-RA formation (30-min incubation, 10 microM atRA, HPLC separation, UV detection 340 nm). The use of 15 cDNA-expressed human P450s from lymphoblast microsomes, showed the formation of 4-OH-RA by CYP3A7 > CYP3A5 > CYP2C18 > CYP2C8 > CYP3A4 > CYP2C9, whereas the 18-OH-RA formation involved CYPs 4A11 > 3A7 > 1A1 > 2C9 > 2C8 > 3A5 > 3A4 >2C18. Kinetic studies identified 3A7 as the most active P450 in the formation of three of the metabolites: for 4-OH-retinoic acid, 3A7 showed a V(max)/K(m) of 127.7, followed by 3A5 (V(max)/K(m) = 25.6), 2C8 (V(max)/K(m) = 24.5), 2C18 (V(max)/K(m) = 15.8), 3A4 (V(max)/K(m) = 5.7), 1A1 (V(max)/K(m) = 5.0), and 4A11 (V(max)/K(m) = 1.9); for 4-oxo-RA, 3A7 showed a V(max)/K(m) of 13.4, followed by a 10-fold lower activity for both 2C18 and 4A11 (V(max)/K(m) = 1.2); and for 18-OH-RA, 3A7 showed a V(max)/K(m) of 10.5 compared with a V(max)/K(m) of 2.1 for 4A11 and 2.0 for 2C8. 5,6-Epoxy-RA was only detected at high substrate concentrations in this system (>10 microM), and P450s 2C8, 2C9, and 1A1 were the most active in its formation. The use of embryonic kidney cells (293) stably transfected with human P450 cDNA confirmed the major involvement of P450s 3A7, 1A1, and 2C8 in the oxidation of atRA, and to a lesser extent, 1A2, 2C9, and 3A4. In conclusion, several human P450s involved in atRA metabolism have been identified, the expression of which was shown to direct atRA metabolism toward the formation of specific metabolites. The role of these human P450s in the biological and anticancer effects of atRA remains to be elucidated. << Less
Mol. Pharmacol. 58:1341-1348(2000) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.