Obtusifoliol (BioDeep_00000001006)

 

Secondary id: BioDeep_00000867771

human metabolite PANOMIX_OTCML-2023 Endogenous natural product


Metabolite Card


(3S,4S,5S,10S,13R,14R,17R)-4,10,13,14-Tetramethyl-17-((R)-6-methyl-5-methyleneheptan-2-yl)-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol

Formula: C30H50O (426.3861)
Chinese Names:
Spectrum Hits: Top Source Homo sapiens(lipidomics) 36.72%

Molecular Structure

SMILES: C1[C@]2(C)C3CC[C@]4(C)[C@@]([H])([C@]([H])(C)CCC(=C)C(C)C)CC[C@@]4(C)C=3CC[C@@]2([H])[C@H](C)[C@@H](O)C1
InChI: InChI=1S/C30H50O/c1-19(2)20(3)9-10-21(4)23-13-17-30(8)26-12-11-24-22(5)27(31)15-16-28(24,6)25(26)14-18-29(23,30)7/h19,21-24,27,31H,3,9-18H2,1-2,4-8H3/t21-,22+,23-,24+,27+,28+,29-,30+/m1/s1

Description

Obtusifoliol belongs to the class of organic compounds known as ergosterols and derivatives. These are steroids containing ergosta-5,7,22-trien-3beta-ol or a derivative thereof, which is based on the 3beta-hydroxylated ergostane skeleton. Thus, obtusifoliol is considered to be a sterol lipid molecule. Obtusifoliol is found, on average, in the highest concentration within evening primroses. Obtusifoliol has also been detected, but not quantified in, several different foods, such as common chokecherries, jicama, pepper (C. frutescens), avocado, and pecan nuts. This could make obtusifoliol a potential biomarker for the consumption of these foods. Obtusifoliol is an intermediate in the biosynthesis of cholesterol: in a reaction catalyzed by the enzyme CYP51A1 (EC 1.14.13.70, sterol 14-demethylase) (PMID: 9559662). CYP51A1 is a housekeeping enzyme essential for the viability of mammals, an essential step in cholesterol biosynthesis. Sterol 14-demethylation occurs in all organisms exhibiting de novo sterol biosynthesis and CYP51A1 has been conserved throughout evolution (PMID: 8797093).
Obtusifoliol is an intermediate in the biosynthesis of cholesterol, in a reaction catalyzed by the enzyme CYP51A1 (EC 1.14.13.70, sterol 14-demethylase). (PMID: 9559662); CYP51A1 is a housekeeping enzyme essential for viability of mammals, essential step in cholesterol biosynthesis; sterol 14-demethylation occurs in all organism exhibiting de novo sterol biosynthesis, and CYP51A1 has been conserved throughout evolution. (PMID: 8797093). Obtusifoliol is found in many foods, some of which are jews ear, mamey sapote, star fruit, and tinda.
Obtusifoliol is a natural product found in Euphorbia chamaesyce, Euphorbia nicaeensis, and other organisms with data available.
Obtusifoliol is a specific CYP51 inhibitor, Obtusifoliol shows the affinity with Kd values of 1.2 μM and 1.4 μM for Trypanosoma brucei (TB) and human CYP51, respectively[1].
Obtusifoliol is a specific CYP51 inhibitor, Obtusifoliol shows the affinity with Kd values of 1.2 μM and 1.4 μM for Trypanosoma brucei (TB) and human CYP51, respectively[1].

Synonyms

30 synonym names

(3S,4S,5S,10S,13R,14R,17R)-4,10,13,14-Tetramethyl-17-((R)-6-methyl-5-methyleneheptan-2-yl)-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol; (3S,4S,5S,10S,13R,14R,17R)-4,10,13,14-tetramethyl-17-[(2R)-6-methyl-5-methylideneheptan-2-yl]-1,2,3,4,5,6,7,11,12,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ol; (2S,5S,6S,7S,11R,14R,15R)-2,6,11,15-tetramethyl-14-[(2R)-6-methyl-5-methylideneheptan-2-yl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-1(10)-en-5-ol; Ergosta-8,24(28)-dien-3-ol, 4,14-dimethyl-, (3.beta.,4.alpha.,5.alpha.)-; 4,14-Dimethylergosta-8,24(28)-dien-3-ol, (3.beta.,4.alpha.,5.alpha.)-; 4.alpha.,14.alpha.-Dimethyl-5.alpha.-ergosta-8,24(28)-dien-3.beta.-ol; 4alpha,14alpha-Dimethyl-24-methylene-5alpha-cholesta-8-en-3beta-ol; Ergosta-8,24(28)-dien-3-ol, 4,14-dimethyl-, (3beta,4alpha,5alpha)-; 5.alpha.-Ergosta-8,24(28)-dien-3.beta.-ol, 4.alpha.,14-dimethyl-; 4α,14α-dimethyl-24-methylene-cholest-8-en-3β-ol; (3beta,4alpha,5alpha)-4,14-Dimethylergosta-8,24(28)-dien-3-ol; 4alpha,14alpha-dimethyl-5alpha-ergosta-8,24(28)-dien-3beta-ol; 4alpha,14alpha-dimethyl-24-methylene-cholest-8-en-3beta-ol; 4,4-Dimethyl-14a-hydroxymethyl-5a-cholesta-8,24-dien-3b-ol; 4alpha,14alpha-Dimethyl-delta8,24(28)-ergostadien-3beta-ol; 4a,14a-Dimethyl-24-methylene-5a-cholesta-8-en-3b-ol; 4α,14α-Dimethyl-24-methylene-5α-cholesta-8-en-3β-ol; (3β,4α,5α)-4,14-Dimethylergosta-8,24(28)-dien-3-ol; 4a,14a-dimethyl-5a-ergosta-8,24(28)-dien-3b-ol; 4α,14α-Dimethyl-5α-ergosta-8,24(28)-dien-3β-ol; 4α,14α-Dimethyl-Δ8,24(28)-ergostadien-3β-ol; EECD77B7-C927-4E6E-B634-DEDFB042A6B9; MMNYKQIDRZNIKT-VSADUBDNSA-N; (+)-OBTUSIFOLIOL; SCHEMBL19270848; UNII-3RH57E39ER; Obtusifoliol; 3RH57E39ER; ST 30:2;O; Obtusifoliol



Cross Reference

24 cross reference id

Classification Terms

Related Pathways

Reactome(0)

BioCyc(2)

PlantCyc(0)

Biological Process

2 related biological process reactions.

Reactome(0)

BioCyc(2)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(0)

PharmGKB(0)

58 organism taxonomy source information

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。

Sub-cellular location Genes
Cytoplasm 9 CAT, CYP2C19, CYP2C9, CYP3A4, DHCR24, MARVELD1, PTGS2, SREBF1, TP53
Peripheral membrane protein 2 CYP1B1, PTGS2
Endosome membrane 1 LDLR
Endoplasmic reticulum membrane 12 CYP1B1, CYP2C19, CYP2C9, CYP3A4, CYP51A1, CYP7A1, DHCR24, HMGCR, HSP90B1, PTGS2, RAC2, SREBF1
Nucleus 7 DHCR24, HSP90B1, MARVELD1, NR1H4, PPARA, SREBF1, TP53
cytosol 5 CAT, HSP90B1, RAC2, SREBF1, TP53
centrosome 1 TP53
nucleoplasm 4 NR1H4, PPARA, SREBF1, TP53
RNA polymerase II transcription regulator complex 1 NR1H4
Cell membrane 2 LDLR, MARVELD1
lamellipodium 1 RAC2
Multi-pass membrane protein 3 HMGCR, MARVELD1, SREBF1
Golgi apparatus membrane 2 DHCR24, SREBF1
cell surface 1 LDLR
Golgi apparatus 1 LDLR
Golgi membrane 2 DHCR24, SREBF1
smooth endoplasmic reticulum 1 HSP90B1
Lysosome 1 LDLR
plasma membrane 5 CYP2C19, CYP2C9, LDLR, MARVELD1, RAC2
Membrane 10 CAT, CYP1B1, CYP3A4, CYP51A1, DHCR24, HMGCR, HSP90B1, LDLR, MARVELD1, TP53
basolateral plasma membrane 1 LDLR
caveola 1 PTGS2
extracellular exosome 3 CAT, HSP90B1, RAC2
endoplasmic reticulum 6 DHCR24, HMGCR, HSP90B1, PTGS2, SREBF1, TP53
extracellular space 2 CRP, IL6
perinuclear region of cytoplasm 1 HSP90B1
mitochondrion 3 CAT, CYP1B1, TP53
protein-containing complex 5 CAT, HSP90B1, PTGS2, SREBF1, TP53
intracellular membrane-bounded organelle 7 CAT, CYP1B1, CYP2C19, CYP2C9, CYP3A4, CYP51A1, CYP7A1
Microsome membrane 6 CYP1B1, CYP2C9, CYP3A4, CYP51A1, CYP7A1, PTGS2
Single-pass type I membrane protein 1 LDLR
Secreted 2 CRP, IL6
extracellular region 4 CAT, CRP, HSP90B1, IL6
Single-pass membrane protein 4 CYP51A1, CYP7A1, DHCR24, LDLR
mitochondrial outer membrane 1 RAC2
Mitochondrion matrix 1 TP53
mitochondrial matrix 2 CAT, TP53
transcription regulator complex 1 TP53
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome 1 TP53
external side of plasma membrane 1 LDLR
low-density lipoprotein particle 1 LDLR
nucleolus 1 TP53
midbody 1 HSP90B1
Early endosome 1 LDLR
Membrane, clathrin-coated pit 1 LDLR
apical part of cell 1 LDLR
clathrin-coated pit 1 LDLR
Cytoplasm, cytoskeleton 2 MARVELD1, TP53
focal adhesion 3 CAT, HSP90B1, RAC2
Peroxisome 1 CAT
Peroxisome matrix 1 CAT
peroxisomal matrix 1 CAT
peroxisomal membrane 2 CAT, HMGCR
Nucleus, PML body 1 TP53
PML body 1 TP53
collagen-containing extracellular matrix 1 HSP90B1
Nucleus inner membrane 1 PTGS2
Nucleus outer membrane 1 PTGS2
nuclear inner membrane 1 PTGS2
nuclear outer membrane 1 PTGS2
Late endosome 1 LDLR
receptor complex 2 LDLR, NR1H4
neuron projection 1 PTGS2
chromatin 4 NR1H4, PPARA, SREBF1, TP53
phagocytic vesicle membrane 1 RAC2
cytoskeleton 1 MARVELD1
[Isoform 3]: Nucleus 1 NR1H4
site of double-strand break 1 TP53
nuclear envelope 2 RAC2, SREBF1
Endomembrane system 1 LDLR
sorting endosome 1 LDLR
Cytoplasmic vesicle membrane 1 SREBF1
Melanosome 1 HSP90B1
euchromatin 1 NR1H4
germ cell nucleus 1 TP53
replication fork 1 TP53
sperm plasma membrane 1 HSP90B1
Peroxisome membrane 1 HMGCR
ficolin-1-rich granule lumen 1 CAT
secretory granule lumen 1 CAT
endoplasmic reticulum lumen 3 HSP90B1, IL6, PTGS2
nuclear matrix 1 TP53
transcription repressor complex 1 TP53
ER to Golgi transport vesicle membrane 1 SREBF1
clathrin-coated endocytic vesicle membrane 1 LDLR
Sarcoplasmic reticulum lumen 1 HSP90B1
[Isoform 2]: Nucleus 1 NR1H4
[Isoform 1]: Nucleus 2 NR1H4, TP53
endolysosome membrane 1 LDLR
somatodendritic compartment 1 LDLR
Cytoplasmic vesicle, COPII-coated vesicle membrane 1 SREBF1
[Isoform 4]: Nucleus 1 NR1H4
endocytic vesicle lumen 1 HSP90B1
PCSK9-LDLR complex 1 LDLR
catalase complex 1 CAT
NADPH oxidase complex 1 RAC2
interleukin-6 receptor complex 1 IL6
endoplasmic reticulum chaperone complex 1 HSP90B1
[Sterol regulatory element-binding protein 1]: Endoplasmic reticulum membrane 1 SREBF1
[Processed sterol regulatory element-binding protein 1]: Nucleus 1 SREBF1
[Isoform SREBP-1aDelta]: Nucleus 1 SREBF1
[Isoform SREBP-1cDelta]: Nucleus 1 SREBF1


Literature Reference

  • Lauren J Salisbury, Stephen J Fletcher, Jeanette E Stok, Luke R Churchman, Joanne T Blanchfield, James J De Voss. Characterization of the cholesterol biosynthetic pathway in Dioscorea transversa. The Journal of biological chemistry. 2023 May; ?(?):104768. doi: 10.1016/j.jbc.2023.104768. [PMID: 37142228]
  • Tatiana Y Hargrove, Laura Friggeri, Zdzislaw Wawrzak, Suneethi Sivakumaran, Eugenia M Yazlovitskaya, Scott W Hiebert, F Peter Guengerich, Michael R Waterman, Galina I Lepesheva. Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design. Journal of lipid research. 2016 08; 57(8):1552-63. doi: 10.1194/jlr.m069229. [PMID: 27313059]
  • Maria Bailen, Mourad Daoubi Khamlichi, Ahmed Benharref, Rafael A Martinez-Diaz, Azucena Gonzalez-Coloma. New Bioactive Semisynthetic Derivatives of 31-Norlanostenol and Obtusifoliol from Euphorbia officinarum. Natural product communications. 2016 Jun; 11(6):733-8. doi: . [PMID: 27534104]
  • Wahid Herchi, Saoussem Harrabi, Khaled Sebei, Sophie Rochut, Sadok Boukhchina, Claude Pepe, Habib Kallel. Phytosterols accumulation in the seeds of Linum usitatissimum L. Plant physiology and biochemistry : PPB. 2009 Oct; 47(10):880-5. doi: 10.1016/j.plaphy.2009.07.001. [PMID: 19616960]
  • Martin O'Brien, Sier-Ching Chantha, Alain Rahier, Daniel P Matton. Lipid signaling in plants. Cloning and expression analysis of the obtusifoliol 14alpha-demethylase from Solanum chacoense Bitt., a pollination- and fertilization-induced gene with both obtusifoliol and lanosterol demethylase activity. Plant physiology. 2005 Oct; 139(2):734-49. doi: 10.1104/pp.105.066639. [PMID: 16169959]
  • Ho Bang Kim, Hubert Schaller, Chang-Hyo Goh, Mi Kwon, Sunghwa Choe, Chung Sun An, Francis Durst, Kenneth A Feldmann, René Feyereisen. Arabidopsis cyp51 mutant shows postembryonic seedling lethality associated with lack of membrane integrity. Plant physiology. 2005 Aug; 138(4):2033-47. doi: 10.1104/pp.105.061598. [PMID: 16040657]
  • Galina I Lepesheva, W David Nes, Wenxu Zhou, George C Hill, Michael R Waterman. CYP51 from Trypanosoma brucei is obtusifoliol-specific. Biochemistry. 2004 Aug; 43(33):10789-99. doi: 10.1021/bi048967t. [PMID: 15311940]
  • D C Lamb, D E Kelly, S L Kelly. Molecular diversity of sterol 14alpha-demethylase substrates in plants, fungi and humans. FEBS letters. 1998 Mar; 425(2):263-5. doi: 10.1016/s0014-5793(98)00247-6. [PMID: 9559662]
  • F Cabello-Hurtado, A Zimmerlin, A Rahier, M Taton, R DeRose, S Nedelkina, Y Batard, F Durst, K E Pallett, D Werck-Reichhart. Cloning and functional expression in yeast of a cDNA coding for an obtusifoliol 14alpha-demethylase (CYP51) in wheat. Biochemical and biophysical research communications. 1997 Jan; 230(2):381-5. doi: 10.1006/bbrc.1996.5873. [PMID: 9016788]
  • R A Kahn, S Bak, C E Olsen, I Svendsen, B L Moller. Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14alpha-demethylase from Sorghum bicolor (L.) Moench. The Journal of biological chemistry. 1996 Dec; 271(51):32944-50. doi: 10.1074/jbc.271.51.32944. [PMID: 8955137]
  • B Grausem, N Chaubet, C Gigot, J C Loper, P Benveniste. Functional expression of Saccharomyces cerevisiae CYP51A1 encoding lanosterol-14-demethylase in tobacco results in bypass of endogenous sterol biosynthetic pathway and resistance to an obtusifoliol-14-demethylase herbicide inhibitor. The Plant journal : for cell and molecular biology. 1995 May; 7(5):761-70. doi: 10.1046/j.1365-313x.1995.07050761.x. [PMID: 7773307]
  • A Rahier, M Taton. Plant sterol biosynthesis: 7-oxo-obtusifoliol analogues as potential selective inhibitors of cytochrome P-450 dependent obtusifoliol 14 alpha-demethylase. Biochimica et biophysica acta. 1992 Apr; 1125(2):215-22. doi: 10.1016/0005-2760(92)90048-z. [PMID: 1571366]
  • Y Aoyama, Y Yoshida. The 4 beta-methyl group of substrate does not affect the activity of lanosterol 14 alpha-demethylase (P-450(14)DM) of yeast: difference between the substrate recognition by yeast and plant sterol 14 alpha-demethylases. Biochemical and biophysical research communications. 1992 Mar; 183(3):1266-72. doi: 10.1016/s0006-291x(05)80327-4. [PMID: 1567403]
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