Mevalonate arm of cholesterol biosynthesis pathway (Homo sapiens)

From WikiPathways

Revision as of 13:51, 4 August 2022 by DeSl (Talk | contribs)
Jump to: navigation, search
2, 311111111, 21CytosolMitochondriaPeroxisomeEndoplasmic reticulumTransportHS-CoAACAT13-hydroxy-3-methylglutaryl-CoAacetoacetateAcetyl-CoAMitochondrial beta-oxidation of fatty acidsdimethylallyl-PPFDFT1HMGCLIDI1NADHFDPSNAD(P)HHMGCS1acetoacetyl-CoAcholesterol synthesisMVKmevaldyl-CoAmevalonatemevalonate-Pmevalonate-PPisopenthyl-PPPMVKMVDgeranyl-PPfamesyl-PPgeranylgeranyl-PPpresqualene-PPsqualeneprotein prenylationGGPS1IDI2GGPS1famesyl-PP3-hydroxy-3-methylglutaryl-CoAmevalonateAcetyl-CoAacetoacetyl-CoA3-hydroxy-3-methylglutaryl-CoAAcetyl-CoAacetoacetyl-CoAACAT1acetoacetateHMGCLACAT2HMGCS1CatalysisPathwayStimulationProteinMetaboliteConversionLegendHMGCRmevaldyl1NAD(P)+HS-CoA1, 22H+NAD(P)HNAD(P)+H+1H+1NAD(P)HNAD(P)+NAD+


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. View the broader scope of cholesterol metabolism at WP430.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

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
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)
H+Metabolite15378 (ChEBI)
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)
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"
Personal tools