Mevalonate arm of cholesterol biosynthesis pathway (Homo sapiens)

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Description

This pathway describes the mevalonate arm of the cholesterol biosynthesis pathway within different cellular regions.

This pathway is also known as the isoprenoid pathway or HMG-CoA reductase pathway, and is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. This pathway produces two five-carbon building blocks (isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP)), which are the precursors for various isoprenoids, a compound class containing cholesterol, vitamin K, coenzyme Q10, and all steroid hormones.

View more details on which drugs are related to these reactions at [WP4189](https://www.wikipathways.org/index.php/Pathway:WP4189). View the broader scope of cholesterol metabolism at [WP430](https://www.wikipathways.org/index.php/Pathway:WP430).

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Quality Tags

Ontology Terms

 

Bibliography

  1. Haines BE, Wiest O, Stauffacher CV; ''The increasingly complex mechanism of HMG-CoA reductase.''; Acc Chem Res, 2013 PubMed Europe PMC Scholia
  2. Benson HE, Watterson S, Sharman JL, Mpamhanga CP, Parton A, Southan C, Harmar AJ, Ghazal P; ''Is systems pharmacology ready to impact upon therapy development? A study on the cholesterol biosynthesis pathway.''; Br J Pharmacol, 2017 PubMed Europe PMC Scholia
  3. Mazein A, Watterson S, Hsieh WY, Griffiths WJ, Ghazal P; ''A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.''; Biochem Pharmacol, 2013 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
140675view18:25, 1 October 2025EgonwAnother markdown link
140674view18:25, 1 October 2025EgonwMarkdown link
140673view18:24, 1 October 2025EgonwRemoved a duplicate description in the GPML
140658view05:54, 29 September 2025EgonwH⁺ with unicode
124024view05:10, 14 September 2022EgonwThe neutral mevaldyl
123596view13:51, 4 August 2022DeSlOntology Term : 'isoprenoid biosynthetic pathway' added !
123595view13:50, 4 August 2022DeSlAdded more details to description.
123594view13:48, 4 August 2022DeSlAdded comments from overlapping content in WP3963
123593view13:45, 4 August 2022DeSlAdded PW link for beta-oxidation of FAs
118431view14:33, 27 May 2021Mkutmonremoved unused reference
117284view10:55, 20 May 2021DeSlUpdated all PW nodes to solid lines again
117283view10:54, 20 May 2021DeSlChecking clickability of double vs single shape PW nodes
116703view13:59, 10 May 2021DeSlUpdated HMGCS1 ID from wikidata to Uniprot
116702view13:57, 10 May 2021DeSlAnnotated ER and cytosol interactions
116701view11:40, 10 May 2021DeSlUpdated with Rhea info until squalene
116700view11:25, 10 May 2021DeSlConnected to Rhea untill geranylgeranyl-PP
116699view11:18, 10 May 2021DeSlUpdated PW DataNode visualisation
116356view18:35, 3 May 2021DeSlUpdated IDs until geranyl-PP
116355view18:30, 3 May 2021DeSlUpdated IDs untill IDI1+2
116354view18:18, 3 May 2021DeSlConnected unconnected lines without removing translocation interactionsheads
116353view18:17, 3 May 2021DeSlReverted to version '07:36, 29 April 2021' by DeSl
116339view12:27, 2 May 2021L DupuisConnected lines
116299view07:36, 29 April 2021DeSlUpdated with Rhea until mevalonate-PP
116298view15:11, 28 April 2021DeSlAdded side metabolites for 3-H-3-MG-CoA to mevalonate interactions
116297view14:57, 28 April 2021DeSlAdded mevaldyl intermediate, including annotation
116296view14:46, 28 April 2021DeSlAdded ID to mevaldyl-CoA, ref to accopanying interactions
116295view13:43, 28 April 2021DeSlAdded lit. refs. for mevaldyl-CoA conversion
116294view13:35, 28 April 2021DeSlReannotated part of PW according to info from Rhea
116293view13:00, 28 April 2021DeSlAdded legend, updated layout
116292view12:48, 28 April 2021DeSlAdded lit ref
104328view13:51, 17 May 2019DeSlModified description
104327view13:50, 17 May 2019DeSlModified description
101730view12:37, 2 November 2018DeSlModified description
101729view12:36, 2 November 2018DeSlModified description
97482view12:50, 23 May 2018Fehrhartfixed connection
96455view11:45, 15 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
95421view13:41, 14 December 2017DeSlOntology Term : 'metabolising cell' added !
95420view13:40, 14 December 2017DeSlOntology Term : 'cell' added !
95419view13:39, 14 December 2017DeSlOntology Term : 'mitochondria transport pathway' added !
95418view13:08, 14 December 2017DeSlOntology Term : 'cholesterol biosynthetic pathway' added !
95417view13:07, 14 December 2017DeSlAdded wikidata as database source where applicable
95416view13:00, 14 December 2017DeSlNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3-hydroxy-3-methylglutaryl-CoAMetaboliteCHEBI:43074 (ChEBI)
ACAT1ProteinP24752 (Uniprot-TrEMBL)
ACAT2ProteinQ9BWD1 (Uniprot-TrEMBL)
Acetyl-CoAMetabolite57288 (ChEBI)
Acetyl-CoAMetaboliteCHEBI:57288 (ChEBI)
FDFT1ProteinP37268 (Uniprot-TrEMBL)
FDPSProteinP14324 (Uniprot-TrEMBL)
GGPS1ProteinO95749 (Uniprot-TrEMBL)
HMGCLProteinP35914 (Uniprot-TrEMBL)
HMGCRProteinP04035 (Uniprot-TrEMBL) Note: 1.1.1.88 is EC class relevant for bacteria, with corresponding Rhea:14833. This Protein has been annotated with the mammalian EC class 1.1.1.34, corresponding Rhea:15989.
HMGCS1ProteinQ01581 (Uniprot-TrEMBL)
HS-CoAMetabolite57287 (ChEBI)
H⁺Metabolite15378 (ChEBI)
IDI1ProteinQ13907 (Uniprot-TrEMBL) TESTCASE: Protein 1 of two individual proteins carrying out the same conversion; same Rhea, diff. kinetic values.
IDI2ProteinQ9BXS1 (Uniprot-TrEMBL) TESTCASE: Protein 2 of two individual proteins carrying out the same conversion; same Rhea, diff. kinetic values.
MVDProteinP53602 (Uniprot-TrEMBL) EC 4.1.1.33
MVKProteinQ03426 (Uniprot-TrEMBL)
Mitochondrial

beta-oxidation of

fatty acids		PathwayWP5241 (WikiPathways)
NAD(P)+MetaboliteCHEBI:18009 (ChEBI)
NAD(P)+MetaboliteCHEBI:58349 (ChEBI)
NAD(P)HMetaboliteCHEBI:16474 (ChEBI)
NAD(P)HMetaboliteCHEBI:57783 (ChEBI)
NAD+Metabolite57540 (ChEBI)
NADHMetabolite57945 (ChEBI)
PMVKProteinQ15126 (Uniprot-TrEMBL)
acetoacetateMetabolite13705 (ChEBI)
acetoacetyl-CoAMetabolite57286 (ChEBI)
acetoacetyl-CoAMetaboliteQ2639429 (Wikidata) TESTCASE: Annotated with ID missing charge; according to Rhea should be CHEBI:57286
cholesterol synthesisPathwayWP197 (WikiPathways)
dimethylallyl-PPMetabolite57623 (ChEBI) AKA Dimethylallyl diphosphate
famesyl-PPMetabolite175763 (ChEBI)
geranyl-PPMetabolite58057 (ChEBI)
geranylgeranyl-PPMetabolite58756 (ChEBI)
isopenthyl-PPMetabolite128769 (ChEBI)
mevaldyl-CoAMetaboliteRGCJQGNQJYHPPZ-FMMSQWOCSA-I (InChIKey)
  • Annotated through ChemSpider API [https://www.chemspider.com/InChI.asmx], starting from SMILES: C[C@](O)(CC([O-])=O)CC(O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12 ; converted to InCHI and then to InCHIKey
  • "hemithioacetal, most likely the prominent reaction intermediate" [PMID:23898905]
mevaldylMetaboliteQ113961354 (Wikidata)
  • Annotated through ChemSpider API [https://www.chemspider.com/InChI.asmx], starting from SMILES: C[C@@](O)(CC=O)CC([O-])=O ; converted to InCHI and then to InCHIKey
  • "aldehyde intermediate, which has never been detected experimentally" [PMID:23898905]
mevalonate-PMetabolite58146 (ChEBI) AKA (R)-5-phosphomevalonate
mevalonate-PPMetaboliteCHEBI:57557 (ChEBI) AKA (R)-5-diphosphomevalonate
mevalonateMetaboliteCHEBI:36464 (ChEBI) Annotated with (R)-mevalonate ID
presqualene-PPMetabolite57310 (ChEBI)
protein prenylationPathway
squaleneMetaboliteQ407560 (Wikidata) TESTCASE: correct mapping from Wikidata to ChEBI-ID (based on Rhea)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
3-hydroxy-3-methylglutaryl-CoAAcetyl-CoAmim-conversion24405 (Rhea)
3-hydroxy-3-methylglutaryl-CoAmevalonatemim-conversion15991 (Rhea)
Acetyl-CoA3-hydroxy-3-methylglutaryl-CoAmim-conversion10190 (Rhea) TESTCASE: Annotated with Rhea ID in opposite direction; should be RHEA:10189
Acetyl-CoAacetoacetyl-CoAmim-conversion21037 (Rhea) TESTCASE: side metabolite not connected to conversion interaction (compared to ACAT1 interaction)
Acetyl-CoAmim-conversion10189 (Rhea)
HS-CoAmim-conversion21037 (Rhea)
NAD(P)+mim-conversion22233 (Rhea)
NAD(P)Hmim-conversion22233 (Rhea)
acetoacetatemim-conversion24405 (Rhea)
acetoacetyl-CoA3-hydroxy-3-methylglutaryl-CoAmim-conversion10189 (Rhea)
dimethylallyl-PPgeranyl-PPmim-conversion22409 (Rhea) TESTCASE: Substrate 2 out of two, which is needed for conversion, directly connected to product.
famesyl-PPgeranylgeranyl-PPmim-conversion17654 (Rhea)
famesyl-PPpresqualene-PPmim-conversion22673 (Rhea)
geranyl-PPfamesyl-PPmim-conversion19362 (Rhea) TESTCASE: Substrate 1 out of two, which is needed for conversion, connected directly to product, includes anchor to connect substrate 2-> product.
isopenthyl-PPdimethylallyl-PPmim-conversion23285 (Rhea)
isopenthyl-PPgeranyl-PPmim-conversion22409 (Rhea) TESTCASE: Substrate 1 out of two, which is needed for conversion, directly connected to product.
isopenthyl-PPmim-conversion17654 (Rhea)
isopenthyl-PPmim-conversion19362 (Rhea) TESTCASE: Substrate 2 out of two, which is needed for conversion, connected to product via anchor from substrate 1-> product.
mevalonate-PPisopenthyl-PPmim-conversion23733 (Rhea)
mevalonate-Pmevalonate-PPmim-conversion16342 (Rhea)
mevalonatemevalonate-Pmim-conversion17066 (Rhea)
presqualene-PPsqualenemim-conversion22233 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4190"
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