Cholesterol synthesis disorders (Homo sapiens)
From WikiPathways
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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- Toth MJ, Huwyler L; ''Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
- Herdendorf TJ, Miziorko HM; ''Phosphomevalonate kinase: functional investigation of the recombinant human enzyme.''; Biochemistry, 2006 PubMed Europe PMC Scholia
- 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
- Fernández C, Suárez Y, Ferruelo AJ, Gómez-Coronado D, Lasunción MA; ''Inhibition of cholesterol biosynthesis by Delta22-unsaturated phytosterols via competitive inhibition of sterol Delta24-reductase in mammalian cells.''; Biochem J, 2002 PubMed Europe PMC Scholia
- DEMPSEY ME, SEATON JD, SCHROEPFER GJ Jr, TROCKMAN RW; ''THE INTERMEDIARY ROLE OF DELTA-5,7-CHOLESTADIEN-3-BETA-OL IN CHOLESTEROL BIOSYNTHESIS.''; J Biol Chem, 1964 PubMed Europe PMC Scholia
- Potter D, Miziorko HM; ''Identification of catalytic residues in human mevalonate kinase.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
- Pandit J, Danley DE, Schulte GK, Mazzalupo S, Pauly TA, Hayward CM, Hamanaka ES, Thompson JF, Harwood HJ Jr; ''Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
- 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
- Herdendorf TJ, Miziorko HM; ''Functional evaluation of conserved basic residues in human phosphomevalonate kinase.''; Biochemistry, 2007 PubMed Europe PMC Scholia
- 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
- Hinson DD, Chambliss KL, Toth MJ, Tanaka RD, Gibson KM; ''Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways.''; J Lipid Res, 1997 PubMed Europe PMC Scholia
- Kuzuguchi T, Morita Y, Sagami I, Sagami H, Ogura K; ''Human geranylgeranyl diphosphate synthase. cDNA cloning and expression.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
- 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
- Tansey TR, Shechter I; ''Structure and regulation of mammalian squalene synthase.''; Biochim Biophys Acta, 2000 PubMed Europe PMC Scholia
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- Laden BP, Tang Y, Porter TD; ''Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase.''; Arch Biochem Biophys, 2000 PubMed Europe PMC Scholia
- 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
- Hedl M, Rodwell VW; ''Inhibition of the class II HMG-CoA reductase of Pseudomonas mevalonii.''; Protein Sci, 2004 PubMed Europe PMC Scholia
- 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
- Rardin MJ, He W, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B, Uppala R, Fitch M, Riiff T, Zhu L, Zhou J, Mulhern D, Stevens RD, Ilkayeva OR, Newgard CB, Jacobson MP, Hellerstein M, Goetzman ES, Gibson BW, Verdin E; ''SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks.''; Cell Metab, 2013 PubMed Europe PMC Scholia
- 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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- 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
- 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
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
(R)-Mevalonic acid 5-phosphate | Metabolite | CHEBI:17436 (ChEBI) | |
(S)-2,3-epoxysqualene | Metabolite | CHEBI:15441 (ChEBI) | |
(r)-mevalonic acid-5-pyrophosphate | Metabolite | Q33061105 (Wikidata) | |
7-Dehydrocholesterol | Metabolite | HMDB00032 (HMDB) | |
Acetyl-CoA | Metabolite | HMDB01206 (HMDB) | |
CYP51A1 | GeneProduct | ENSG00000001630 (Ensembl) | |
Cholesterol biosynthesis pathway | Pathway | WP197 (WikiPathways) | |
DHCR24 | GeneProduct | ENSG00000116133 (Ensembl) | |
DHCR7 | GeneProduct | ENSG00000172893 (Ensembl) | |
Desmosterol | Metabolite | CHEBI:17737 (ChEBI) | |
Dimethylallyl pyrophosphate | Metabolite | CHEBI:16057 (ChEBI) | |
EBP | GeneProduct | ENSG00000147155 (Ensembl) | |
FDFT1 | GeneProduct | ENSG00000079459 (Ensembl) | |
FDPS | GeneProduct | ENSG00000160752 (Ensembl) | |
Farnesyl pyrophosphate | Metabolite | HMDB00961 (HMDB) | |
Geranyl-PP | Metabolite | HMDB01285 (HMDB) | |
HMG-CoA | Metabolite | CHEBI:15467 (ChEBI) | |
HMGCR | GeneProduct | ENSG00000113161 (Ensembl) | |
HMGCS1 | GeneProduct | ENSG00000112972 (Ensembl) | |
HSD3B2 | GeneProduct | ENSG00000203859 (Ensembl) | |
IDI1 | GeneProduct | ENSG00000067064 (Ensembl) | |
LBR | GeneProduct | ENSG00000143815 (Ensembl) | |
LSS | GeneProduct | ENSG00000160285 (Ensembl) | |
Lathosterol | Metabolite | CHEBI:17168 (ChEBI) | |
MSMO1 | GeneProduct | ENSG00000052802 (Ensembl) | |
MVD | GeneProduct | ENSG00000167508 (Ensembl) | |
MVK | GeneProduct | ENSG00000110921 (Ensembl) | |
Mevalonic acid | Metabolite | HMDB00227 (HMDB) | |
PMVK | GeneProduct | ENSG00000163344 (Ensembl) | |
SC5D | GeneProduct | ENSG00000109929 (Ensembl) | |
SQLE | GeneProduct | ENSG00000104549 (Ensembl) | |
Zymosterol | Metabolite | CHEBI:18252 (ChEBI) | |
beta oxidation | Pathway | WP5193 (WikiPathways) | |
cholesterol | Metabolite | CHEBI:16113 (ChEBI) | |
isopentenyl pyrophosphate | Metabolite | CHEBI:128769 (ChEBI) | |
lanosterol | Metabolite | CHEBI:16521 (ChEBI) | |
squalene | Metabolite | Q407560 (Wikidata) |
Annotated Interactions
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Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
(R)-Mevalonic acid 5-phosphate | (r)-mevalonic acid-5-pyrophosphate | mim-conversion | 16341 (Rhea) | |
(S)-2,3-epoxysqualene | lanosterol | mim-conversion | 14621 (Rhea) | |
(r)-mevalonic acid-5-pyrophosphate | isopentenyl pyrophosphate | mim-conversion | 23732 (Rhea) | |
7-Dehydrocholesterol | cholesterol | mim-conversion | 23984 (Rhea) | |
Acetyl-CoA | HMG-CoA | mim-conversion | 10188 (Rhea) | |
Desmosterol | cholesterol | mim-conversion | 36391 (Rhea) | |
Dimethylallyl pyrophosphate | Geranyl-PP | mim-conversion | 22408 (Rhea) | |
Farnesyl pyrophosphate | squalene | mim-conversion | 32295 (Rhea) | |
Geranyl-PP | Farnesyl pyrophosphate | mim-conversion | 23300 (Rhea) | |
HMG-CoA | Mevalonic acid | mim-conversion | 14833 (Rhea) | |
Lathosterol | 7-Dehydrocholesterol | mim-conversion | 23984 (Rhea) | |
Mevalonic acid | (R)-Mevalonic acid 5-phosphate | mim-conversion | 17065 (Rhea) | |
isopentenyl pyrophosphate | Dimethylallyl pyrophosphate | mim-conversion | 23284 (Rhea) | |
isopentenyl pyrophosphate | mim-conversion | 17653 (Rhea) | ||
isopentenyl pyrophosphate | mim-conversion | 25694 (Rhea) | ||
lanosterol | Lathosterol | mim-conversion | 14621 (Rhea) | |
squalene | (S)-2,3-epoxysqualene | mim-conversion | 25282 (Rhea) |