Mevalonate arm of cholesterol biosynthesis pathway (WP4190)
Homo sapiens
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-KutmonActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
cholesterol biosynthetic pathway mitochondria transport pathway altered cholesterol biosynthetic pathway isoprenoid biosynthetic pathwayCell Type Ontology
cell obsolete metabolising cell| 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) |
| famesyl-PP | Metabolite | chebi:175763 | |
| 3-hydroxy-3-methylglutaryl-CoA | Metabolite | chebi:43074 | Annotated with (3S) IDaka HMG-CoA |
| mevalonate | Metabolite | chebi:36464 | Annotated with (R)-mevalonate ID |
| Acetyl-CoA | Metabolite | chebi:57288 | |
| acetoacetyl-CoA | Metabolite | chebi:57286 | |
| 3-hydroxy-3-methylglutaryl-CoA | Metabolite | chebi:43074 | |
| Acetyl-CoA | Metabolite | chebi:57288 | |
| acetoacetyl-CoA | Metabolite | chebi:57286 | |
| acetoacetate | Metabolite | chebi:13705 | |
| 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:16474 | |
| NAD(P)+ | Metabolite | chebi:18009 | |
| H+ | Metabolite | chebi:15378 | |
| 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. |
| GGPS1 | Protein | uniprot:O95749 | |
| ACAT1 | Protein | uniprot:P24752 | |
| HMGCL | Protein | uniprot:P35914 | |
| ACAT2 | Protein | uniprot:Q9BWD1 | |
| HMGCS1 | Protein | uniprot:Q01581 | |
| 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
- 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
- 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
- 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