Cholesterol synthesis disorders (Homo sapiens)

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1, 8, 9212023254, 12-146, 16, 2224152113, 10, 1719181957Disease or deficiencySLOSdesmosterolosisGene ProductABSLegendCTRCT44GeneProductDiseaseCDPX2Metabolitelinked to a diseaseHEMMEVACatalyst reactionConversion reactionCHILDCYP51 deficiencyMSMO1lathosterolosisAPMR4MetaboliteLSSEBPAcetyl-CoA(R)-Mevalonic acid 5-phosphateMVKDHCR7LathosterolFDFT1LBR7-DehydrocholesterolHMGCRcholesterolHMG-CoAPMVKMevalonic acidCholesterol biosynthesis pathwayZymosterolDesmosterolMVDbeta oxidationDHCR24MSMO1(S)-2,3-epoxysqualeneHSD3B2lanosterolSC5D(r)-mevalonic acid-5-pyrophosphateFarnesyl pyrophosphateIDI1SQLEFDPSCYP51A1Dimethylallyl pyrophosphateGeranyl-PPsqualeneHMGCS1isopentenyl pyrophosphateFDPSCKHYPT14SQSDPOROK9POROK7POROK1


Cholesterol is synthesized via a cascade of enzymatic reactions known as the mevalonate pathway. This series of reactions is primarily regulated by a rate-limiting step involving the conversion of hydroxyl-methyl glutaryl-coenzyme A (HMG-CoA) into mevalonate. In this pathway multiple diseases and disorders involving the cholesterol synthesis are included and its role depicted in the pathway.

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Ontology Terms



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  1. Laden BP, Tang Y, Porter TD; ''Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase.''; Arch Biochem Biophys, 2000 PubMed Europe PMC Scholia
  2. Hedl M, Rodwell VW; ''Inhibition of the class II HMG-CoA reductase of Pseudomonas mevalonii.''; Protein Sci, 2004 PubMed Europe PMC Scholia
  3. Blagg BS, Jarstfer MB, Rogers DH, Poulter CD; ''Recombinant squalene synthase. A mechanism for the rearrangement of presqualene diphosphate to squalene.''; J Am Chem Soc, 2002 PubMed Europe PMC Scholia
  4. Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM; ''Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  5. Kavanagh KL, Dunford JE, Bunkoczi G, Russell RGG, Oppermann U; ''The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding.''; J Biol Chem, 2006 PubMed Europe PMC Scholia
  6. Zerenturk EJ, Kristiana I, Gill S, Brown AJ; ''The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1).''; Biochim Biophys Acta, 2012 PubMed Europe PMC Scholia
  7. Ramos-Valdivia AC, van der Heijden R, Verpoorte R; ''Isopentenyl diphosphate isomerase: a core enzyme in isoprenoid biosynthesis. A review of its biochemistry and function.''; Nat Prod Rep, 1997 PubMed Europe PMC Scholia
  8. Lee HK, Zheng YF, Xiao XY, Bai M, Sakakibara J, Ono T, Prestwich GD; ''Photoaffinity labeling identifies the substrate-binding site of mammalian squalene epoxidase.''; Biochem Biophys Res Commun, 2004 PubMed Europe PMC Scholia
  9. Liu Y, Yao ZX, Papadopoulos V; ''Cytochrome P450 17alpha hydroxylase/17,20 lyase (CYP17) function in cholesterol biosynthesis: identification of squalene monooxygenase (epoxidase) activity associated with CYP17 in Leydig cells.''; Mol Endocrinol, 2005 PubMed Europe PMC Scholia
  10. Pandit J, Danley DE, Schulte GK, Mazzalupo S, Pauly TA, Hayward CM, Hamanaka ES, Thompson JF, Harwood HJ Jr; ''Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  11. Toth MJ, Huwyler L; ''Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  12. Herdendorf TJ, Miziorko HM; ''Phosphomevalonate kinase: functional investigation of the recombinant human enzyme.''; Biochemistry, 2006 PubMed Europe PMC Scholia
  13. Hinson DD, Chambliss KL, Toth MJ, Tanaka RD, Gibson KM; ''Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways.''; J Lipid Res, 1997 PubMed Europe PMC Scholia
  14. Herdendorf TJ, Miziorko HM; ''Functional evaluation of conserved basic residues in human phosphomevalonate kinase.''; Biochemistry, 2007 PubMed Europe PMC Scholia
  15. Bae SH, Lee JN, Fitzky BU, Seong J, Paik YK; ''Cholesterol biosynthesis from lanosterol. Molecular cloning, tissue distribution, expression, chromosomal localization, and regulation of rat 7-dehydrocholesterol reductase, a Smith-Lemli-Opitz syndrome-related protein.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  16. Fernández C, Suárez Y, Ferruelo AJ, Gómez-Coronado D, Lasunción MA; ''Inhibition of cholesterol biosynthesis by Delta22-unsaturated phytosterols via competitive inhibition of sterol Delta24-reductase in mammalian cells.''; Biochem J, 2002 PubMed Europe PMC Scholia
  17. Tansey TR, Shechter I; ''Structure and regulation of mammalian squalene synthase.''; Biochim Biophys Acta, 2000 PubMed Europe PMC Scholia
  19. Yamamoto S, Lin K, Bloch K; ''''; , PubMed Europe PMC Scholia
  20. Rardin MJ, He W, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B, Uppala R, Fitch M, Riiff T, Zhu L, Zhou J, Mulhern D, Stevens RD, Ilkayeva OR, Newgard CB, Jacobson MP, Hellerstein M, Goetzman ES, Gibson BW, Verdin E; ''SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks.''; Cell Metab, 2013 PubMed Europe PMC Scholia
  21. Ambo T, Noike M, Kurokawa H, Koyama T; ''Cloning and functional analysis of novel short-chain cis-prenyltransferases.''; Biochem Biophys Res Commun, 2008 PubMed Europe PMC Scholia
  22. Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, FitzPatrick DR, Kelley RI, Wanders RJ; ''Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis.''; Am J Hum Genet, 2001 PubMed Europe PMC Scholia
  23. Kuzuguchi T, Morita Y, Sagami I, Sagami H, Ogura K; ''Human geranylgeranyl diphosphate synthase. cDNA cloning and expression.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  24. Potter D, Miziorko HM; ''Identification of catalytic residues in human mevalonate kinase.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  25. Sillero MA, de Diego A, Tavares JE, Silva JA, Pérez-Zúñiga FJ, Sillero A; ''Synthesis of ATP derivatives of compounds of the mevalonate pathway (isopentenyl di- and triphosphate; geranyl di- and triphosphate, farnesyl di- and triphosphate, and dimethylallyl diphosphate) catalyzed by T4 RNA ligase, T4 DNA ligase and other ligases Potential relationship with the effect of bisphosphonates on osteoclasts.''; Biochem Pharmacol, 2009 PubMed Europe PMC Scholia


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122440view08:10, 6 April 2022FehrhartModified title
122365view19:51, 23 March 2022DeSlOntology Term : 'DOID:4' removed !
122363view13:54, 23 March 2022EvelinePeterseAnother rhea interaction and literature was added
122362view13:36, 23 March 2022EvelinePetersechanged some interactions
122361view11:12, 23 March 2022EvelinePeterseadded a Rhea interaction and literature to a reaction
122258view13:36, 16 March 2022EvelinePetersepathway reference added
122255view13:24, 16 March 2022EvelinePetersechanged the name of disease and changed the layout
122252view12:40, 16 March 2022EvelinePeterseOntology Term : 'Smith-Lemli-Opitz syndrome' added !
122251view12:38, 16 March 2022EvelinePeterseOntology Term : 'X-linked chondrodysplasia punctata 2' added !
122250view12:37, 16 March 2022EvelinePeterseOntology Term : 'Antley-Bixler syndrome' added !
122249view12:31, 16 March 2022EvelinePeterseOntology Term : 'alopecia-mental retardation syndrome 4' added !
122248view12:30, 16 March 2022EvelinePeterseOntology Term : 'cataract 44' added !
122247view12:30, 16 March 2022EvelinePeterseOntology Term : 'hypotrichosis 14' added !
122245view12:23, 16 March 2022EvelinePeterseOntology Term : 'porokeratosis' added !
122244view12:22, 16 March 2022EvelinePeterseOntology Term : 'mevalonic aciduria' added !
122243view12:22, 16 March 2022EvelinePeterseOntology Term : 'PW:0001346' removed !
122242view12:21, 16 March 2022EvelinePetersechanged a line
122241view12:20, 16 March 2022EvelinePeterseChanged a disease
122240view12:18, 16 March 2022EvelinePeterseOntology Term : 'PW:0001346' removed !
122239view11:08, 16 March 2022EvelinePeterseadjusted some connections
122238view11:02, 16 March 2022EvelinePeterseadjusted my legend
122237view10:53, 16 March 2022EvelinePeterseadjusted the lines
122236view10:49, 16 March 2022EvelinePeterseconnected all the lines
122235view10:47, 16 March 2022EvelinePeterseadded some diseases
122234view10:36, 16 March 2022EvelinePetersedatanode pathway has changed
122232view10:31, 16 March 2022EvelinePeterseOntology Term : 'PW:0001346' removed !
122228view10:26, 16 March 2022EvelinePeterseadded some disorders for LSS
122206view16:05, 15 March 2022EvelinePetersedeleted references
122205view15:54, 15 March 2022EvelinePetersechanged some references
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122199view15:01, 15 March 2022EvelinePetersechanged some references
122197view14:40, 15 March 2022EvelinePetersechanged some references
122196view14:35, 15 March 2022EvelinePeterseDeleted some Datanodes
122195view14:26, 15 March 2022EvelinePetersechanged some arrows in mim conversions
122193view14:14, 15 March 2022EvelinePeterseOmin links adjusted
122101view22:53, 10 March 2022DeSlMade legend more neath
122100view22:51, 10 March 2022DeSlUpdate layout
121798view14:06, 5 March 2022EvelinePeterseadded the parts better into the cell
121797view13:57, 5 March 2022EvelinePeterseModified description
121796view13:55, 5 March 2022EvelinePeterseOntology Term : 'Disease' added !
121795view13:52, 5 March 2022EvelinePeterseOntology Term : 'CHILD syndrome' added !
121794view13:51, 5 March 2022EvelinePeterseOntology Term : 'Greenberg dysplasia' added !
121793view13:46, 5 March 2022EvelinePeterseOntology Term : 'desmosterolosis pathway' added !
121792view13:43, 5 March 2022EvelinePeterseOntology Term : 'cholesterol metabolic pathway' added !
121791view13:43, 5 March 2022EvelinePeterseOntology Term : 'cholesterol transport pathway' added !
121790view13:43, 5 March 2022EvelinePeterseOntology Term : 'altered cholesterol biosynthetic pathway' added !

External references


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NameTypeDatabase referenceComment
(R)-Mevalonic acid 5-phosphateMetaboliteCHEBI:17436 (ChEBI)
(S)-2,3-epoxysqualeneMetaboliteCHEBI:15441 (ChEBI)
(r)-mevalonic acid-5-pyrophosphateMetaboliteQ33061105 (Wikidata)
7-DehydrocholesterolMetaboliteHMDB00032 (HMDB)
Acetyl-CoAMetaboliteHMDB01206 (HMDB)
CYP51A1GeneProductENSG00000001630 (Ensembl)
Cholesterol biosynthesis pathwayPathwayWP197 (WikiPathways)
DHCR24GeneProductENSG00000116133 (Ensembl)
DHCR7GeneProductENSG00000172893 (Ensembl)
DesmosterolMetaboliteCHEBI:17737 (ChEBI)
Dimethylallyl pyrophosphateMetaboliteCHEBI:16057 (ChEBI)
EBPGeneProductENSG00000147155 (Ensembl)
FDFT1GeneProductENSG00000079459 (Ensembl)
FDPSGeneProductENSG00000160752 (Ensembl)
Farnesyl pyrophosphateMetaboliteHMDB00961 (HMDB)
Geranyl-PPMetaboliteHMDB01285 (HMDB)
HMG-CoAMetaboliteCHEBI:15467 (ChEBI)
HMGCRGeneProductENSG00000113161 (Ensembl)
HMGCS1GeneProductENSG00000112972 (Ensembl)
HSD3B2GeneProductENSG00000203859 (Ensembl)
IDI1GeneProductENSG00000067064 (Ensembl)
LBRGeneProductENSG00000143815 (Ensembl)
LSSGeneProductENSG00000160285 (Ensembl)
LathosterolMetaboliteCHEBI:17168 (ChEBI)
MSMO1GeneProductENSG00000052802 (Ensembl)
MVDGeneProductENSG00000167508 (Ensembl)
MVKGeneProductENSG00000110921 (Ensembl)
Mevalonic acidMetaboliteHMDB00227 (HMDB)
PMVKGeneProductENSG00000163344 (Ensembl)
SC5DGeneProductENSG00000109929 (Ensembl)
SQLEGeneProductENSG00000104549 (Ensembl)
ZymosterolMetaboliteCHEBI:18252 (ChEBI)
beta oxidation PathwayWP5193 (WikiPathways)
cholesterolMetaboliteCHEBI:16113 (ChEBI)
isopentenyl pyrophosphateMetaboliteCHEBI:128769 (ChEBI)
lanosterolMetaboliteCHEBI:16521 (ChEBI)
squaleneMetaboliteQ407560 (Wikidata)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(R)-Mevalonic acid 5-phosphate(r)-mevalonic acid-5-pyrophosphatemim-conversion16341 (Rhea)
(S)-2,3-epoxysqualenelanosterolmim-conversion14621 (Rhea)
(r)-mevalonic acid-5-pyrophosphateisopentenyl pyrophosphatemim-conversion23732 (Rhea)
7-Dehydrocholesterolcholesterolmim-conversion23984 (Rhea)
Acetyl-CoAHMG-CoAmim-conversion10188 (Rhea)
Desmosterolcholesterolmim-conversion36391 (Rhea)
Dimethylallyl pyrophosphateGeranyl-PPmim-conversion22408 (Rhea)
Farnesyl pyrophosphatesqualenemim-conversion32295 (Rhea)
Geranyl-PPFarnesyl pyrophosphatemim-conversion23300 (Rhea)
HMG-CoAMevalonic acidmim-conversion14833 (Rhea)
Lathosterol7-Dehydrocholesterolmim-conversion23984 (Rhea)
Mevalonic acid(R)-Mevalonic acid 5-phosphatemim-conversion17065 (Rhea)
isopentenyl pyrophosphateDimethylallyl pyrophosphatemim-conversion23284 (Rhea)
isopentenyl pyrophosphatemim-conversion17653 (Rhea)
isopentenyl pyrophosphatemim-conversion25694 (Rhea)
lanosterolLathosterolmim-conversion14621 (Rhea)
squalene(S)-2,3-epoxysqualenemim-conversion25282 (Rhea)
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