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


Description

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

 

Bibliography

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  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
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  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
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  17. Tansey TR, Shechter I; ''Structure and regulation of mammalian squalene synthase.''; Biochim Biophys Acta, 2000 PubMed Europe PMC Scholia
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  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
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  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

History

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CompareRevisionActionTimeUserComment
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
122204view15:47, 15 March 2022EvelinePetersechanged some references
122203view15:36, 15 March 2022EvelinePeterseadded some references
122202view15:31, 15 March 2022EvelinePetersechanged some references
122201view15:25, 15 March 2022EvelinePetersechanged some references
122200view15:11, 15 March 2022EvelinePetersechanged some references
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

DataNodes

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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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