Enzymes
| UniProtKB help_outline | 5 proteins |
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- Name help_outline lathosterol Identifier CHEBI:17168 (CAS: 80-99-9) help_outline Charge 0 Formula C27H46O InChIKeyhelp_outline IZVFFXVYBHFIHY-SKCNUYALSA-N SMILEShelp_outline [H][C@@]12CC=C3[C@]4([H])CC[C@]([H])([C@H](C)CCCC(C)C)[C@@]4(C)CC[C@]3([H])[C@@]1(C)CC[C@H](O)C2 2D coordinates Mol file for the small molecule Search links Involved in 6 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5α-cholest-8-en-3β-ol Identifier CHEBI:16608 (CAS: 566-97-2) help_outline Charge 0 Formula C27H46O InChIKeyhelp_outline QETLKNDKQOXZRP-XTGBIJOFSA-N SMILEShelp_outline [H][C@@]12CCC3=C(CC[C@]4(C)[C@]([H])(CC[C@@]34[H])[C@H](C)CCCC(C)C)[C@@]1(C)CC[C@H](O)C2 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
Cross-references
| RHEA:15281 | RHEA:15282 | RHEA:15283 | RHEA:15284 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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The reversibility of the delta8-cholestenol-delta7-cholestenol isomerase reaction in cholesterol biosynthesis.
Wilton D.C., Rahimtula A.D., Akhtar M.
The incubation of Delta(7)-cholestenol with a 10000g supernatant or 105000g microsomes in the presence of tritiated water is studied. The reisolated Delta(7)-cholestenol contained up to 0.67g.atom of tritium/mole. This result can best be explained by assuming the reversibility of the reaction Delt ... >> More
The incubation of Delta(7)-cholestenol with a 10000g supernatant or 105000g microsomes in the presence of tritiated water is studied. The reisolated Delta(7)-cholestenol contained up to 0.67g.atom of tritium/mole. This result can best be explained by assuming the reversibility of the reaction Delta(8)-cholestenol right harpoon over left harpoon Delta(7)-cholestenol. << Less
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Purification, characterization and catalytic properties of human sterol 8-isomerase.
Nes W.D., Zhou W., Dennis A.L., Li H., Jia Z., Keith R.A., Piser T.M., Furlong S.T.
CHO 2, encoding human sterol 8-isomerase (hSI), was introduced into plasmids pYX213 or pET23a. The resulting native protein was overexpressed in erg 2 yeast cells and purified to apparent homogeneity. The enzyme exhibited a K (m) of 50 microM and a turnover number of 0.423 s(-1) for zymosterol, an ... >> More
CHO 2, encoding human sterol 8-isomerase (hSI), was introduced into plasmids pYX213 or pET23a. The resulting native protein was overexpressed in erg 2 yeast cells and purified to apparent homogeneity. The enzyme exhibited a K (m) of 50 microM and a turnover number of 0.423 s(-1) for zymosterol, an isoelectric point of 7.70, a native molecular mass of 107000 Da and was tetrameric. The structural features of zymosterol provided optimal substrate acceptability. Biomimetic studies of acid-catalysed isomerization of zymosterol resulted in formation of cholest-8(14)-enol, whereas the enzyme-generated product was a Delta(7)-sterol, suggesting absolute stereochemical control of the reaction by hSI. Using (2)H(2)O and either zymosterol or cholesta-7,24-dienol as substrates, the reversibility of the reaction was confirmed by GC-MS of the deuterated products. The positional specific incorporation of deuterium at C-9alpha was established by a combination of (1)H- and (13)C-NMR analyses of the enzyme-generated cholesta-7,24-dienol. Kinetic analyses indicated the reaction equilibrium ( K (eq)=14; DeltaG(o')=-6.5 kJ/mol) for double-bond isomerization favoured the forward direction, Delta(8) to Delta(7). Treatment of hSI with different high-energy intermediate analogues produced the following dissociation constants ( K (i)): emopamil (2 microM)=tamoxifen (1 microM)=tridemorph (1 microM)<25-azacholesterol (21 microM) <ketoconazole (156 microM)<cholesterol (620 microM). The results were consistent with stereoelectronic features of isomerization and support the general model for Delta(7)-sterol formation in cholesterol synthesis. << Less
Biochem J 367:587-599(2002) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Emopamil-binding protein, a mammalian protein that binds a series of structurally diverse neuroprotective agents, exhibits delta8-delta7 sterol isomerase activity in yeast.
Silve S., Dupuy P.H., Labit-Lebouteiller C., Kaghad M., Chalon P., Rahier A., Taton M., Lupker J., Shire D., Loison G.
Delta8-delta7 sterol isomerase is an essential enzyme on the sterol biosynthesis pathway in eukaryotes. This endoplasmic reticulum-resident membrane protein catalyzes the conversion of delta8-sterols to their corresponding delta7-isomers. No sequence data for high eukaryote sterol isomerase being ... >> More
Delta8-delta7 sterol isomerase is an essential enzyme on the sterol biosynthesis pathway in eukaryotes. This endoplasmic reticulum-resident membrane protein catalyzes the conversion of delta8-sterols to their corresponding delta7-isomers. No sequence data for high eukaryote sterol isomerase being available so far, we have cloned a murine sterol isomerase-encoding cDNA by functional complementation of the corresponding deficiency in the yeast Saccharomyces cerevisiae. The amino acid sequence deduced from the cDNA open reading frame is highly similar to human emopamil-binding protein (EBP), a protein of unknown function that constitutes a molecular target for neuroprotective drugs. A yeast strain in which the sterol isomerase coding sequence has been replaced by that of human EBP or its murine homologue recovers the ability to convert delta8-sterol into delta7-sterol, both in vivo and in vitro. In these recombinant strains, both cell proliferation and the sterol isomerization reaction are inhibited by the high affinity EBP ligand trifluoperazine, as is the case in mammalian cells but not in wild type yeast cell. In contrast, the recombinant strains are much less susceptible to the sterol inhibition effect of haloperidol and fenpropimorph, as compared with wild type yeast strains. Our results strongly suggest that EBP and delta8-delta7 sterol isomerase are identical proteins in mammals. << Less
J. Biol. Chem. 271:22434-22440(1996) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.