Reaction participants Show >> << Hide
- Name help_outline all-trans-retinol Identifier CHEBI:17336 (Beilstein: 403040; CAS: 11103-57-4,68-26-8) help_outline Charge 0 Formula C20H30O InChIKeyhelp_outline FPIPGXGPPPQFEQ-OVSJKPMPSA-N SMILEShelp_outline C\C(=C/CO)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C 2D coordinates Mol file for the small molecule Search links Involved in 29 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 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 [adrenodoxin]
Identifier
RHEA-COMP:9998
Reactive part
help_outline
- Name help_outline [2Fe-2S]1+ Identifier CHEBI:33738 Charge 1 Formula Fe2S2 InChIKeyhelp_outline MAGIRAZQQVQNKP-UHFFFAOYSA-N SMILEShelp_outline S1[Fe]S[Fe+]1 2D coordinates Mol file for the small molecule Search links Involved in 236 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline all-trans-3-hydroxyretinol Identifier CHEBI:156530 (CAS: 6890-93-3) help_outline Charge 0 Formula C20H30O2 InChIKeyhelp_outline OBODKGDXEIUEIH-DAWLFQHYSA-N SMILEShelp_outline C\C(=C/CO)\C=C\C=C(/C)\C=C\C1=C(C)CC(O)CC1(C)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 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 [adrenodoxin]
Identifier
RHEA-COMP:9999
Reactive part
help_outline
- Name help_outline [2Fe-2S]2+ Identifier CHEBI:33737 Charge 2 Formula Fe2S2 InChIKeyhelp_outline XSOVBBGAMBLACL-UHFFFAOYSA-N SMILEShelp_outline S1[Fe+]S[Fe+]1 2D coordinates Mol file for the small molecule Search links Involved in 236 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:65520 | RHEA:65521 | RHEA:65522 | RHEA:65523 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially desaturates trans-retinol to 3,4-dehydroretinol.
Johnson K.M., Phan T.T.N., Albertolle M.E., Guengerich F.P.
Recently, zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway. We show by proteomic analysis ... >> More
Recently, zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway. We show by proteomic analysis that P450 27C1 is localized to human skin, with two proteins of different sizes present, one being a cleavage product of the full-length form. P450 27C1 oxidized all-<i>trans</i>-retinol to 3,4-dehydroretinol, 4-hydroxy (OH) retinol, and 3-OH retinol in a 100:3:2 ratio. Neither 3-OH nor 4-OH retinol was an intermediate in desaturation. No kinetic burst was observed in the steady state; neither the rate of substrate binding nor product release was rate-limiting. Ferric P450 27C1 reduction by adrenodoxin was 3-fold faster in the presence of the substrate and was ∼5-fold faster than the overall turnover. Kinetic isotope effects of 1.5-2.3 (on <i>k</i><sub>cat</sub>/<i>K<sub>m</sub></i> ) were observed with 3,3-, 4,4-, and 3,3,4,4-deuterated retinol. Deuteration at C-4 produced a 4-fold increase in 3-hydroxylation due to metabolic switching, with no observable effect on 4-hydroxylation. Deuteration at C-3 produced a strong kinetic isotope effect for 3-hydroxylation but not 4-hydroxylation. Analysis of the products of deuterated retinol showed a lack of scrambling of a putative allylic radical at C-3 and C-4. We conclude that the most likely catalytic mechanism begins with abstraction of a hydrogen atom from C-4 (or possibly C-3) initiating the desaturation pathway, followed by a sequential abstraction of a hydrogen atom or proton-coupled electron transfer. Adrenodoxin reduction and hydrogen abstraction both contribute to rate limitation. << Less
J. Biol. Chem. 292:13672-13687(2017) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.