Mevalonate arm of cholesterol biosynthesis pathway (WP4190)

Homo sapiens

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he mevalonate arm of the cholesterol biosynthesis pathway for different cellular regions.

Authors

Denise Slenter , Egon Willighagen , Friederike Ehrhart , Lauren J. Dupuis , and Martina Summer-Kutmon

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

cholesterol biosynthetic pathway mitochondria transport pathway altered cholesterol biosynthetic pathway isoprenoid biosynthetic pathway

Cell Type Ontology

cell obsolete metabolising cell

Participants
Query Drugst.One

Label Type Compact URI Comment
dimethylallyl-PP Metabolite chebi:57623 AKA Dimethylallyl diphosphate
NAD(P)H Metabolite chebi:16474
acetoacetate Metabolite chebi:13705
HS-CoA Metabolite chebi:57287 Added due to information present in Rhea
Acetyl-CoA Metabolite chebi:57288
NADH Metabolite chebi:57945
3-hydroxy-3-methylglutaryl-CoA Metabolite chebi:43074 Annotated with (3S) ID
acetoacetyl-CoA Metabolite wikidata:Q2639429 TESTCASE: Annotated with ID missing charge; according to Rhea should be CHEBI:57286
mevaldyl-CoA Metabolite inchikey:RGCJQGNQJYHPPZ-FMMSQWOCSA-I 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]
mevalonate Metabolite chebi:36464 Annotated with (R)-mevalonate ID
mevalonate-P Metabolite chebi:58146 AKA (R)-5-phosphomevalonate
mevalonate-PP Metabolite chebi:57557 AKA (R)-5-diphosphomevalonate
isopenthyl-PP Metabolite chebi:128769
geranyl-PP Metabolite chebi:58057
famesyl-PP Metabolite chebi:175763
geranylgeranyl-PP Metabolite chebi:58756
presqualene-PP Metabolite chebi:57310
squalene Metabolite wikidata:Q407560 TESTCASE: correct mapping from Wikidata to ChEBI-ID (based on Rhea)
3-hydroxy-3-methylglutaryl-CoA Metabolite chebi:43074 Annotated with (3S) ID
aka HMG-CoA
acetoacetyl-CoA Metabolite chebi:57286
3-hydroxy-3-methylglutaryl-CoA Metabolite chebi:43074
mevaldyl Metabolite wikidata:Q113961354 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]
NAD(P)+ Metabolite chebi:18009
HS-CoA Metabolite chebi:57287
H+ Metabolite chebi:15378
NAD(P)H Metabolite chebi:57783
NAD(P)+ Metabolite chebi:58349
NAD+ Metabolite chebi:57540
FDFT1 Protein uniprot:P37268
ACAT1 Protein uniprot:P24752
HMGCL Protein uniprot:P35914
HMGCS1 Protein uniprot:Q01581
IDI1 Protein uniprot:Q13907 TESTCASE: Protein 1 of two individual proteins carrying out the same conversion; same Rhea, diff. kinetic values.
MVK Protein uniprot:Q03426
FDPS Protein uniprot:P14324
PMVK Protein uniprot:Q15126
MVD Protein uniprot:P53602 EC 4.1.1.33
GGPS1 Protein uniprot:O95749
IDI2 Protein uniprot:Q9BXS1 TESTCASE: Protein 2 of two individual proteins carrying out the same conversion; same Rhea, diff. kinetic values.
ACAT2 Protein uniprot:Q9BWD1
HMGCR Protein uniprot:P04035 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.

References

  1. A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway. Mazein A, Watterson S, Hsieh WY, Griffiths WJ, Ghazal P. Biochem Pharmacol. 2013 Jul 1;86(1):56–66. PubMed Europe PMC Scholia
  2. The increasingly complex mechanism of HMG-CoA reductase. Haines BE, Wiest O, Stauffacher CV. Acc Chem Res. 2013 Nov 19;46(11):2416–26. PubMed Europe PMC Scholia
  3. Is systems pharmacology ready to impact upon therapy development? A study on the cholesterol biosynthesis pathway. Benson HE, Watterson S, Sharman JL, Mpamhanga CP, Parton A, Southan C, et al. Br J Pharmacol. 2017 Dec;174(23):4362–82. PubMed Europe PMC Scholia