Lanosterol

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Lanosterol
Ball-and-stick model of lanosterol
Names
IUPAC name
Lanosta-8,24-dien-3β-ol
Systematic IUPAC name
(1R,3aR,5aR,7S,9aS,11aR)-3a,6,6,9a,11a-Pentamethyl-1-[(2R)-6-methylhept-5-en-2-yl]-2,3,3a,4,5,5a,6,7,8,9,9a,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
Identifiers
3D model (JSmol)
2226449
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.001.105 Edit this at Wikidata
EC Number
  • 201-214-9
KEGG
MeSH Lanosterol
UNII
  • InChI=1S/C30H50O/c1-20(2)10-9-11-21(3)22-14-18-30(8)24-12-13-25-27(4,5)26(31)16-17-28(25,6)23(24)15-19-29(22,30)7/h10,21-22,25-26,31H,9,11-19H2,1-8H3/t21-,22-,25+,26+,28-,29-,30+/m1/s1 checkY
    Key: CAHGCLMLTWQZNJ-BQNIITSRSA-N checkY
  • InChI=1/C30H50O/c1-20(2)10-9-11-21(3)22-14-18-30(8)24-12-13-25-27(4,5)26(31)16-17-28(25,6)23(24)15-19-29(22,30)7/h10,21-22,25-26,31H,9,11-19H2,1-8H3/t21-,22-,25+,26+,28-,29-,30+/m1/s1
    Key: CAHGCLMLTWQZNJ-BQNIITSRBP
  • C[C@H](CCC=C(C)C)[C@H]1CC[C@]2(C)C1CCC3=C2CC[C@H]4C(C)(C)[C@@H](O)CC[C@]34C
Properties
C30H50O
Molar mass 426.71 g/mol
Melting point 138 to 140 °C (280 to 284 °F; 411 to 413 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Lanosterol is a tetracyclic triterpenoid and is the compound from which all animal and fungal steroids are derived. By contrast, plant steroids are produced via cycloartenol.[1]

Role in the biosynthesis of other steroids[edit]

Elaboration of lanosterol under enzyme catalysis leads to the core structure of steroids. 14-Demethylation of lanosterol by CYP51 eventually yields cholesterol.[2]

Simplified version of the lanosterol synthesis pathway with the intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP), and squalene shown. Some intermediates are omitted.

Biosynthesis[edit]

Description Illustration Enzyme
Two molecules of farnesyl pyrophosphate condense with reduction by NADPH to form squalene squalene synthase
Squalene is oxidized to 2,3-oxidosqualene (squalene epoxide) squalene monooxygenase
2,3-Oxidosqualene is converted to a protosterol cation and finally to lanosterol lanosterol synthase
(step 2) (step 2)

Research[edit]

Lanosterol has been identified as a key component in maintaining eye lens clarity.[3] Pre-clinical research has identified Lanosterol as a possible agent for the reversal and prevention of cataracts.[4] In vivo experiments on dogs showed significant reversal of cataracts within 6 weeks of lanosterol injection.[5] In 2018, Lanosterol was shown to improve lens clarity in cells with lens clouding due to aging or physical stressors.[6] A subsequent study in 2022 by Kehao Wang, Hoshino, Kentaro Uesugi, Naoto Yagi, Pierscionek and Andley found positive results on the optics of the lens in mice with cataracts.[7]

Use[edit]

Lanosterol is an ingredient in over-the-counter ophthalmic products to prevent cataracts. However, the solubility and bioavailability of lanosterol is not conducive to aqueous formulations.[8] Heliostatix Biotechnology claims to have a method of solubilizing lanosterol for use in aqueous products.[9]

See also[edit]

References[edit]

  1. ^ Schaller, Hubert (May 2003). "The role of sterols in plant growth and development". Progress in Lipid Research. 42 (3): 163–175. doi:10.1016/S0163-7827(02)00047-4. PMID 12689617.
  2. ^ "Do Lanosterol eye drops work for dogs? - PetACS Pet Health Products". petacs.com. Retrieved 2023-06-06.
  3. ^ Huff, M; Telford, D (July 2005). "Lord of the rings – the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear". Trends in Pharmacological Sciences. 26 (7): 335–340. doi:10.1016/j.tips.2005.05.004. PMID 15951028.
  4. ^ Zhang, K.; Zhao, L.; Zhu, J.; Hou, R.; Wang, S.; Yan, Y. (2016). "Lanosterol reversal of protein aggregation in cataract". Acta Ophthalmologica. 94. doi:10.1111/j.1755-3768.2016.0033.
  5. ^ Zhao, Ling; Chen, Xiang-Jun; Zhu, Jie; Xi, Yi-Bo; Yang, Xu; Hu, Li-Dan; Ouyang, Hong; Patel, Sherrina H.; Jin, Xin; Lin, Danni; Wu, Frances; Flagg, Ken; Cai, Huimin; Li, Gen; Cao, Guiqun; Lin, Ying; Chen, Daniel; Wen, Cindy; Chung, Christopher; Wang, Yandong; Qiu, Austin; Yeh, Emily; Wang, Wenqiu; Hu, Xun; Grob, Seanna; Abagyan, Ruben; Su, Zhiguang; Tjondro, Harry Christianto; Zhao, Xi-Juan; Luo, Hongrong; Hou, Rui; Jefferson, J.; Perry, P.; Gao, Weiwei; Kozak, Igor; Granet, David; Li, Yingrui; Sun, Xiaodong; Wang, Jun; Zhang, Liangfang; Liu, Yizhi; Yan, Yong-Bin; Zhang, Kang (July 2015). "Lanosterol reverses protein aggregation in cataracts". Nature. 523 (7562): 607–611. Bibcode:2015Natur.523..607Z. doi:10.1038/nature14650. PMID 26200341. S2CID 4469138.
  6. ^ Shen, Xinyue; Zhu, Manhui; Kang, Lihua; Tu, Yuanyuan; Li, Lele; Zhang, Rutan; Qin, Bai; Yang, Mei; Guan, Huaijin (11 July 2018). "Lanosterol Synthase Pathway Alleviates Lens Opacity in Age-Related Cortical Cataract". Journal of Ophthalmology. 2018: 1–9. doi:10.1155/2018/4125893. PMC 6079410. PMID 30116630.
  7. ^ Wang, Kehao; Hoshino, Masato; Uesugi, Kentaro; Yagi, Naoto; Pierscionek, Barbara K.; Andley, Usha P. (2022-05-16). "Oxysterol Compounds in Mouse Mutant αA- and αB-Crystallin Lenses Can Improve the Optical Properties of the Lens". Investigative Ophthalmology & Visual Science. 63 (5): 15. doi:10.1167/iovs.63.5.15. ISSN 1552-5783. PMC 9123516. PMID 35575904.
  8. ^ Daszynski, Damian M.; Santhoshkumar, Puttur; Phadte, Ashutosh S.; Sharma, K. Krishna; Zhong, Haizhen A.; Lou, Marjorie F.; Kador, Peter F. (2019). "Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts". Scientific Reports. 9 (1): 8459. Bibcode:2019NatSR...9.8459D. doi:10.1038/s41598-019-44676-4. PMC 6560215. PMID 31186457.
  9. ^ Heliostatix.org

Further reading[edit]

External links[edit]