View source for Lanosterol synthase

{{Short description|Mammalian protein found in Homo sapiens}}
{{cs1 config|name-list-style=vanc}}
{{infobox enzyme
| Name       = lanosterol synthase
| EC_number  = 5.4.99.7
| CAS_number = 9032-71-7
| GO_code    = 0000250
| image      =
| width      = 
| caption    =  
}}
{{Infobox_gene}}

'''Lanosterol synthase''' ({{EnzExplorer|5.4.99.7}}) is an oxidosqualene [[cyclase]] (OSC) [[enzyme]] that converts [[2,3-Oxidosqualene|(''S'')-2,3-oxidosqualene]] to a protosterol cation and finally to [[lanosterol]].<ref name="pmid6027261">{{cite journal | vauthors = Dean PD, Ortiz de Montellano PR, Bloch K, Corey EJ | title = A soluble 2,3-oxidosqualene sterol cyclase | journal = The Journal of Biological Chemistry | volume = 242 | issue = 12 | pages = 3014–5 | date = Jun 1967 | doi = 10.1016/S0021-9258(18)99606-7 | pmid = 6027261 | url = http://www.jbc.org/content/242/12/3014.abstract | doi-access = free }}</ref> [[Lanosterol]] is a key four-ringed intermediate in [[cholesterol]] biosynthesis.<ref name="one">{{cite journal | vauthors = Huff MW, Telford DE | title = Lord of the rings--the mechanism for oxidosqualene:lanosterol cyclase becomes crystal clear | journal = Trends in Pharmacological Sciences | volume = 26 | issue = 7 | pages = 335–340 | date = Jul 2005 | pmid = 15951028 | doi = 10.1016/j.tips.2005.05.004 | url = http://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(05)00127-6 }}</ref><ref name="nineteen">{{cite journal | vauthors = Yamamoto S, Lin K, Bloch K | title = Some properties of the microsomal 2,3-oxidosqualene sterol cyclase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 63 | issue = 1 | pages = 110–7 | date = May 1969 | pmid = 5257956 | doi=10.1073/pnas.63.1.110 | pmc=534008| bibcode = 1969PNAS...63..110Y | doi-access = free }}</ref> In humans, lanosterol synthase is encoded by the ''LSS'' [[gene]].<ref name="pmid7639730">{{cite journal | vauthors = Baker CH, Matsuda SP, Liu DR, Corey EJ | title = Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library | journal = Biochemical and Biophysical Research Communications | volume = 213 | issue = 1 | pages = 154–160 | date = Aug 1995 | pmid = 7639730 | doi = 10.1006/bbrc.1995.2110 }}</ref><ref name="pmid8655142">{{cite journal|last1=Young|first1=Michele|last2=Chen|first2=Haiming|last3=Lalioti|first3=Maria D.|last4=Antonarakis|first4=Stylianos E.|title=The human lanosterol synthase gene maps to chromosome 21q22.3|journal=Human Genetics|date=May 1996|volume=97|issue=5|pages=620–624|doi=10.1007/BF02281872|pmid=8655142|s2cid=21051816}}</ref>

In [[eukaryotes]], lanosterol synthase is an [[integral monotopic protein]] associated with the [[cytosolic]] side of the [[endoplasmic reticulum]].<ref name="four">{{cite journal | vauthors = Ruf A, Müller F, D'Arcy B, Stihle M, Kusznir E, Handschin C, Morand OH, Thoma R | title = The monotopic membrane protein human oxidosqualene cyclase is active as monomer | journal = Biochemical and Biophysical Research Communications | volume = 315 | issue = 2 | pages = 247–254 | date = Mar 2004 | pmid = 14766201 | doi = 10.1016/j.bbrc.2004.01.052 }}</ref> Some evidence suggests that the [[enzyme]] is a soluble, non-[[membrane-bound|membrane bound]] [[protein]] in the few [[prokaryotes]] that produce it.<ref name="eighteen">{{cite journal | vauthors = Lamb DC, Jackson CJ, Warrilow AG, Manning NJ, Kelly DE, Kelly SL | title = Lanosterol biosynthesis in the prokaryote Methylococcus capsulatus: insight into the evolution of sterol biosynthesis | journal = Molecular Biology and Evolution | volume = 24 | issue = 8 | pages = 1714–1721 | date = Aug 2007 | pmid = 17567593 | doi = 10.1093/molbev/msm090 | doi-access = free }}</ref>

Due to the enzyme's role in [[cholesterol]] biosynthesis, there is interest in lanosterol synthase [[enzyme inhibitor|inhibitors]] as potential cholesterol-reducing drugs, to complement existing [[statins]].<ref name="three">{{cite journal | vauthors = Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A | title = Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase | journal = Nature | volume = 432 | issue = 7013 | pages = 118–122 | date = Nov 2004 | pmid = 15525992 | doi = 10.1038/nature02993 | bibcode = 2004Natur.432..118T | s2cid = 364281 }}</ref>

==Mechanism==
[[File:Lanosterol Synthase Mech.tif|thumb|200 px|left|alt=Full-length profile.|'''Figure 1:''' Lanosterol synthase mechanism. The discrete carbocation intermediates show the non-concerted nature of the mechanism.]]
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Though some data on the mechanism has been obtained by the use of [[suicide inhibition|suicide inhibitors]], [[site-directed mutagenesis|mutagenesis]] studies, and [[homology modeling]], it is still not fully understood how the [[enzyme]] catalyzes the formation of [[lanosterol]].<ref name="three" />

===Initial epoxide protonation and ring opening===
{{See also|protonation}}
Before the acquisition of the protein's [[X-ray crystal structure]], [[site-directed mutagenesis]] was used to determine residues key to the enzyme's catalytic activity. It was determined that an [[aspartic acid]] residue (D455) and two [[histidine]] residues (H146 and H234) were essential to enzyme function. ''Corey et al.'' hypothesized that the aspartic acid acts by protonating the substrate's [[epoxide]] ring, thus increasing its susceptibility to [[Intramolecular reaction|intramolecular]] attack by the nearest [[double bond]], with H146 possibly intensifying the proton donor ability of the aspartic acid through [[hydrogen bonding]].<ref name="six">{{cite journal | vauthors = Corey EJ, Cheng CH, Baker CH, Matsuda SP, Li D, Song X  | title = Studies on the Substrate Binding Segments and Catalytic Action of Lanosterol Synthase. Affinity Labeling with Carbocations Derived from Mechanism-Based Analogs of 2, 3-Oxidosqualene and Site-Directed Mutagenesis Probes | journal = J. Am. Chem. Soc. | volume = 119 | issue =6| pages = 1289–96 |date=February 1997 | doi = 10.1021/ja963228o}}</ref> After acquisition of the [[X-ray crystal structure]] of the enzyme, the role of D455 as a proton donor to the substrate's epoxide was confirmed, though it was found that D455 is more likely stabilized by hydrogen bonding from two [[cysteine]] residues (C456 and C533) than from the earlier suggested histidine.<ref name="three" />

===Ring formation cascade===
Epoxide protonation activates the substrate, setting off a cascade of ring forming reactions. Four rings in total (A through D) are formed, producing the [[cholesterol]] backbone.<ref name="three" />  Though the idea of a concerted formation of all four rings had been entertained in the past, kinetic studies with [[2,3-Oxidosqualene|(''S'')-2,3-oxidosqualene]] analogs showed that product formation is achieved through discrete [[carbocation]] intermediates (see '''Figure 1'''). Isolation of monocyclic and bicyclic products from lanosterol synthase mutants has further weakened the hypothesis of a concerted mechanism.<ref name="eight">{{cite journal | vauthors = Wu TK, Wang TT, Chang CH, Liu YT, Shie WS | title = Importance of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase tyrosine 707 residue for chair-boat bicyclic ring formation and deprotonation reactions | journal = Organic Letters | volume = 10 | issue = 21 | pages = 4959–62 | date = Nov 2008 | pmid = 18842050 | doi = 10.1021/ol802036c }}</ref><ref name="nine">{{cite journal | vauthors = Joubert BM, Hua L, Matsuda SP | title = Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation | journal = Organic Letters | volume = 2 | issue = 3 | pages = 339–41 | date = Feb 2000 | pmid = 10814317 | doi = 10.1021/ol9912940 }}</ref> Evidence suggests that epoxide ring opening and A ring formation is concerted, though.<ref name="seven">{{cite journal | vauthors = Corey EJ, Cheng CH, Baker CH, Matsuda SP, Li D, Song X  | title = Methodology for the Preparation of Pure Recombinant S. cerevisiae Lanosterol Synthase Using a Baculovirus Expression System. Evidence That Oxirane Cleavage and A-Ring Formation Are Concerted in the Biosynthesis of Lanosterol from 2,3-Oxidosqualene | journal = J. Am. Chem. Soc. | volume = 119 | issue = 6| pages = 1277–88 |date=February 1997 | doi = 10.1021/ja963227w}}</ref>

==Structure==
Lanosterol synthase is a two-domain monomeric protein<ref name="four" /> composed of two connected (α/α) barrel domains and three smaller [[beta barrel|β-structures]]. The enzyme [[active site]] is in the center of the protein, closed off by a constricted channel. Passage of the (''S'')-2,3-epoxysqualene substrate through the channel requires a change in [[protein conformation]]. In [[eukaryotes]], a [[hydrophobic]] surface (6% of the total enzyme surface area) is the [[Endoplasmic reticulum|ER]] membrane-binding region (see '''Figure 2''').<ref name="three" />

The enzyme contains five fingerprint regions containing [[Glutamine|Gln]]-[[tryptophan|Trp]] motifs, which are also present in the highly analogous bacterial enzyme [[squalene-hopene cyclase]].<ref name="three" />   Residues of these fingerprint regions contain stacked sidechains which are thought to contribute to enzyme stability during the highly [[exergonic reaction|exergonic]] cyclization reactions catalyzed by the enzyme.<ref name="ten">{{cite journal | vauthors = Wendt KU, Poralla K, Schulz GE | title = Structure and function of a squalene cyclase | journal = Science | volume = 277 | issue = 5333 | pages = 1811–15 | date = Sep 1997 | pmid = 9295270 | doi = 10.1126/science.277.5333.1811 }}</ref>

==Function==

===Catalysis of lanosterol formation===
Lanosterol synthase catalyzes the conversion of [[2,3-Oxidosqualene|(''S'')-2,3-epoxysqualene]] to [[lanosterol]], a key four-ringed intermediate in [[cholesterol]] biosynthesis.<ref name="one" /><ref name="nineteen" /> Thus, it in turn provides the precursor to [[estrogen]]s, [[androgen]]s, [[progestogen]]s, [[glucocorticoids]], [[mineralocorticoid]]s, and [[neurosteroid]]s. In [[eukaryotes]] the enzyme is bound to the [[cytosolic]] side of the [[endoplasmic reticulum]] membrane.<ref name="four" />  While [[cholesterol]] synthesis is mostly associated with [[eukaryotes]], few [[prokaryotes]] have been found to express lanosterol synthase; it has been found as a soluble protein in ''[[Methylococcus capsulatus]]''.<ref name="eighteen" />

===Catalysis of epoxylanosterol formation===
Lanosterol synthase also catalyzes the cyclization of 2,3;22,23-diepoxysqualene to 24(''S''),25-epoxylanosterol,<ref name="eleven">{{cite journal | vauthors = Corey EJ, Gross SK | title = Formation of sterols by the action of 2,3-oxidosqualene-sterol cyclase on the factitious substrates 2,3:22,23-dioxidosqualene and 2,3-oxido-22,23-dihydrosqualene | journal = Journal of the American Chemical Society | volume = 89 | issue = 17 | pages = 4561–2 | date = Aug 1967 | pmid = 6046552 | doi = 10.1021/ja00993a079 }}</ref> which is later converted to 24(''S''),25-epoxycholesterol.<ref name="twelve">{{cite journal | vauthors = Nelson JA, Steckbeck SR, Spencer TA | title = Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide | journal = The Journal of Biological Chemistry | volume = 256 | issue = 3 | pages = 1067–8 | date = Feb 1981 | doi = 10.1016/S0021-9258(19)69921-7 | pmid = 7451488 | doi-access = free }}</ref> Since the enzyme affinity for this second [[Substrate (biochemistry)|substrate]] is greater than for the monoepoxy (''S'')-2,3-epoxysqualene, under partial inhibition conversion of 2,3;22,23-diepoxysqualene to 24(''S''),25-epoxylanosterol is favored over [[lanosterol]] synthesis.<ref name="thirteen">{{cite journal | vauthors = Boutaud O, Dolis D, Schuber F | title = Preferential cyclization of 2,3(S):22(S),23-dioxidosqualene by mammalian 2,3-oxidosqualene-lanosterol cyclase | journal = Biochemical and Biophysical Research Communications | volume = 188 | issue = 2 | pages = 898–904 | date = Oct 1992 | pmid = 1445330 | doi = 10.1016/0006-291X(92)91140-L }}</ref> This has relevance for disease prevention and treatment.

==Clinical significance==

===Enzyme inhibitors as cholesterol-lowering drugs===
Interest has grown in lanosterol synthase inhibitors as drugs to lower blood cholesterol and treat [[atherosclerosis]]. The widely popular [[statin]] drugs currently used to lower [[low-density lipoprotein|LDL (low-density lipoprotein) cholesterol]] function by inhibiting [[HMG-CoA reductase]] activity.<ref name="one" /> Because this enzyme catalyzes the formation of precursors far upstream of [[2,3-oxidosqualene|(''S'')-2,3-epoxysqualene]] and cholesterol, [[statins]] may negatively influence amounts of intermediates required for other biosynthetic pathways (e.g. synthesis of [[isoprenoids]], [[coenzyme Q]]). Thus, lanosterol synthase, which is more closely tied to cholesterol biosynthesis than [[HMG-CoA reductase]], is an attractive drug target.<ref name="fifteen">{{cite journal | vauthors = Telford DE, Lipson SM, Barrett PH, Sutherland BG, Edwards JY, Aebi JD, Dehmlow H, Morand OH, Huff MW | title = A novel inhibitor of oxidosqualene:lanosterol cyclase inhibits very low-density lipoprotein apolipoprotein B100 (apoB100) production and enhances low-density lipoprotein apoB100 catabolism through marked reduction in hepatic cholesterol content | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 25 | issue = 12 | pages = 2608–14 | date = Dec 2005 | pmid = 16210564 | doi = 10.1161/01.ATV.0000189158.28455.94 | doi-access = free }}</ref>

Lanosterol synthase inhibitors are thought to lower [[LDL]] and [[VLDL]] cholesterol by a dual control mechanism. Studies in which lanosterol synthase is partially inhibited have shown both a direct decrease in [[lanosterol]] formation and a decrease in [[HMG-CoA reductase]] activity. The [[oxysterol]] 24(''S''),25-epoxylanosterol, which is preferentially formed over [[lanosterol]] during partial lanosterol synthase inhibition, is believed to be responsible for this inhibition of [[HMG-CoA reductase]] activity.<ref name="fourteen">{{cite journal | vauthors = Panini SR, Gupta A, Sexton RC, Parish EJ, Rudney H | title = Regulation of sterol biosynthesis and of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in cultured cells by progesterone | journal = The Journal of Biological Chemistry | volume = 262 | issue = 30 | pages = 14435–40 | date = Oct 1987 | doi = 10.1016/S0021-9258(18)47813-1 | pmid = 3667583 | doi-access = free }}</ref>

==Evolution==
It is believed that [[oxidosqualene cyclase]]s (OSCs, the class to which lanosterol cyclase belongs) evolved from bacterial squalene-hopene cyclase (SHC), which is involved with the formation of [[hopanoids]]. [[Phylogenetic trees]] constructed from the amino acid sequences of OSCs in diverse organisms suggest a single common ancestor, and that the synthesis pathway evolved only once.<ref name="sixteen">{{cite journal | vauthors = Pearson A, Budin M, Brocks JJ | title = Phylogenetic and biochemical evidence for sterol synthesis in the bacterium Gemmata obscuriglobus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 26 | pages = 15352–7 | date = Dec 2003 | pmid = 14660793 | pmc = 307571 | doi = 10.1073/pnas.2536559100 | bibcode = 2003PNAS..10015352P | doi-access = free }}</ref> The discovery of [[sterane]]s including [[cholestane]] in 2.7-billion year-old shales from [[Pilbara Craton]], [[Australia]], suggests that [[eukaryotes]] with OSCs and complex steroid machinery were present early in earth's history.<ref name="seventeen">{{cite journal | vauthors = Brocks JJ, Logan GA, Buick R, Summons RE | title = Archean molecular fossils and the early rise of eukaryotes | journal = Science | volume = 285 | issue = 5430 | pages = 1033–6 | date = Aug 1999 | pmid = 10446042 | doi = 10.1126/science.285.5430.1033 | bibcode = 1999Sci...285.1033B | citeseerx = 10.1.1.516.9123 }}</ref>

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin |35em}}
* {{cite journal | vauthors = Roessler E, Mittaz L, Du Y, Scott HS, Chang J, Rossier C, Guipponi M, Matsuda SP, Muenke M, Antonarakis SE | title = Structure of the human Lanosterol synthase gene and its analysis as a candidate for holoprosencephaly (HPE1) | journal = Human Genetics | volume = 105 | issue = 5 | pages = 489–95 | date = Nov 1999 | pmid = 10598817 | doi = 10.1007/s004390051135 | doi-broken-date = 2024-11-02 | url = https://zenodo.org/record/1232966 }}
* {{cite journal | vauthors = Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC | title = Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects | journal = Atherosclerosis | volume = 191 | issue = 1 | pages = 63–72 | date = Mar 2007 | pmid = 16806233 | doi = 10.1016/j.atherosclerosis.2006.05.032 }}
* {{cite journal | vauthors = Beyea MM, Heslop CL, Sawyez CG, Edwards JY, Markle JG, Hegele RA, Huff MW | title = Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol | journal = The Journal of Biological Chemistry | volume = 282 | issue = 8 | pages = 5207–16 | date = Feb 2007 | pmid = 17186944 | doi = 10.1074/jbc.M611063200 | doi-access = free }}
* {{cite journal | vauthors = Dang H, Liu Y, Pang W, Li C, Wang N, Shyy JY, Zhu Y | title = Suppression of 2,3-oxidosqualene cyclase by high fat diet contributes to liver X receptor-alpha-mediated improvement of hepatic lipid profile | journal = The Journal of Biological Chemistry | volume = 284 | issue = 10 | pages = 6218–26 | date = Mar 2009 | pmid = 19119143 | pmc = 2649084 | doi = 10.1074/jbc.M803702200 | doi-access = free }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Sung CK, Shibuya M, Sankawa U, Ebizuka Y | title = Molecular cloning of cDNA encoding human lanosterol synthase | journal = Biological & Pharmaceutical Bulletin | volume = 18 | issue = 10 | pages = 1459–61 | date = Oct 1995 | pmid = 8593458 | doi = 10.1248/bpb.18.1459 | doi-access = free }}
* {{cite journal | vauthors = Young M, Chen H, Lalioti MD, Antonarakis SE | title = The human lanosterol synthase gene maps to chromosome 21q22.3 | journal = Human Genetics | volume = 97 | issue = 5 | pages = 620–4 | date = May 1996 | pmid = 8655142 | doi = 10.1007/BF02281872 | s2cid = 21051816 }}
* {{cite journal | vauthors = Peffley DM, Gayen AK, Morand OH | title = Down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels and synthesis in syrian hamster C100 cells by the oxidosqualene cyclase inhibitor [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4-bromophenyl)-me thanone (Ro 48-8071): comparison to simvastatin | journal = Biochemical Pharmacology | volume = 56 | issue = 4 | pages = 439–49 | date = Aug 1998 | pmid = 9763219 | doi = 10.1016/S0006-2952(98)00083-5 }}
* {{cite journal | vauthors = Lu Y, Dollé ME, Imholz S, van 't Slot R, Verschuren WM, Wijmenga C, Feskens EJ, Boer JM | title = Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations | journal = Journal of Lipid Research | volume = 49 | issue = 12 | pages = 2582–9 | date = Dec 2008 | pmid = 18660489 | doi = 10.1194/jlr.M800232-JLR200 | doi-access = free }}
* {{cite journal | vauthors = Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR | title = Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution | journal = Science | volume = 308 | issue = 5725 | pages = 1149–54 | date = May 2005 | pmid = 15790807 | doi = 10.1126/science.1108625 | bibcode = 2005Sci...308.1149C | s2cid = 13047538 }}
* {{cite journal | vauthors = Pyrah IT, Kalinowski A, Jackson D, Davies W, Davis S, Aldridge A, Greaves P | title = Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse | journal = Toxicologic Pathology | volume = 29 | issue = 2 | pages = 174–9 | year = 2001 | pmid = 11421484 | doi = 10.1080/019262301317052440 | s2cid = 38721319 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
* {{cite journal | vauthors = Ruf A, Müller F, D'Arcy B, Stihle M, Kusznir E, Handschin C, Morand OH, Thoma R | title = The monotopic membrane protein human oxidosqualene cyclase is active as monomer | journal = Biochemical and Biophysical Research Communications | volume = 315 | issue = 2 | pages = 247–54 | date = Mar 2004 | pmid = 14766201 | doi = 10.1016/j.bbrc.2004.01.052 }}
* {{cite journal | vauthors = Mark M, Muller P, Maier R, Eisele B | title = Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells | journal = Journal of Lipid Research | volume = 37 | issue = 1 | pages = 148–58 | date = Jan 1996 | doi = 10.1016/S0022-2275(20)37643-4 | pmid = 8820110 | doi-access = free }}
{{refend}}

== External links ==
* {{MeshName|Lanosterol+synthase}}

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[[Category:Steroid hormone biosynthesis]]
[[Category:EC 5.4.99]]