Cholesterol biosynthesis pathway in hepatocytes (Homo sapiens)

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1-6Vitamin D (Calciferol metabolism)LDLR degradationSterol Eflux4beta-hydroxycholesterolFatty Acid Biosynthesis7alpha-hydroxycholesterolLipoproteins24S-hydroxycholesterol25-hydroxycholesterolPresqualene monophosphate BileSteroid synthesis24,25-epoxycholesterol27-hydroxycholesterolDiepoxy-SqualeneKetogenesisIsopentenyl diphosphatePresqualene diphosphate7-Dehydrocholesterol24,25-DihydrolanosterolCell membranes7-Dehydrodemosterol7-oxocholesterolGGPS1SREBF2SREBF2CP7A1FDPSFDFT1SQLELSSPMVKCYP51A1TM7SF2LBRMSMO1NSDHLMVKHSD17B7EBPNR1H3DHCR7DHCR24SC5DACAT2NR1H3PLPP6HMGCRLBRMSMO1NSDHLHMGCS1HSD17B7TM7SF2IDI2MVDCYP46A1CYP27A1CH25HNR1H2IDI1NR1H2SREBF1SREBF1CholestenoneDihydro-FF-MASAcetoacetyl-CoAMevalonate-PPDihydro-T-MASMevalonate-PT-MASZymosterolMevalonic acidZymostenolHMGCS2HMGCS1ACAT2FASNACSL1ACSL3ACSL4ELOVL2ELOVL3ELOVL4ELOVL5FADS1FADS2SCDACOT1ACOT2FF-MASCholestadienolMYLIPABCG1ABCA1DesmosterolACAT2HMGCS1DMAPPHMGCS2FASNACSL1ACSL3ACSL4ELOVL2ELOVL3ELOVL4ELOVL5FADS1FADS2SCDACOT1ACOT2Acetyl-CoAHMG-CoAGPPFAPPSQNESQOXLNSOLCholesterolLathosterolABCA1ABCG1MYLIPMg2+NucleusHepatocyte


Description

This pathway was constructed based on the Brown et al 2021 book chapter (Cholesterol Synthesis), combined with the Reactome Cholesterol Synthesis pathway (DOI:10.3180/R-HSA-191273.7) and the WikiPathways WP4718 (Cholesterol metabolism with Bloch and Kandutsch-Russell pathways (Homo sapiens)). Additional information was incorporated based on the literature. All protein were curated for cell-specific (hepatocyte) isoforms.

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Quality Tags

Ontology Terms

 

Bibliography

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  1. Song BL, Javitt NB, DeBose-Boyd RA; ''Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol.''; Cell Metab, 2005 PubMed Europe PMC Scholia
  2. Brown, Andrew J., W. Coates, Hudson, J. Sharpe, Laura; ''Chapter 10 - Cholesterol synthesis''; Biochemistry of Lipids, Lipoproteins and Membranes (Seventh Edition) , 2021
  3. Rudney H, Sexton RC; ''Regulation of cholesterol biosynthesis.''; Annu Rev Nutr, 1986 PubMed Europe PMC Scholia
  4. Russell DW; ''Cholesterol biosynthesis and metabolism.''; Cardiovasc Drugs Ther, 1992 PubMed Europe PMC Scholia
  5. Gaylor JL; ''Membrane-bound enzymes of cholesterol synthesis from lanosterol.''; Biochem Biophys Res Commun, 2002 PubMed Europe PMC Scholia
  6. Herman GE; ''Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.''; Hum Mol Genet, 2003 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
135219view11:35, 8 August 2024EweitzClear cache to fix board dimensions
135218view11:34, 8 August 2024EweitzEconomize layout
135217view11:33, 8 August 2024EweitzStandardize cell components
134467view00:38, 22 July 2024EweitzContain nucleus completely inside hepatocyte, economize layout
126886view05:41, 30 June 2023EgonwFixed the WikiPathways datasources
125908view16:16, 17 March 2023JmillanacostaAdded bibliography from the literature in description
125762view10:46, 9 March 2023DeSlUpdated last MIMconversion to arrows for PW nodes
125761view10:44, 9 March 2023DeSlUpdated more MIMconversion to arrows for PW nodes
125760view10:44, 9 March 2023DeSlChanging MIM-Conversion to arrow if pointing toward pathway node
125759view10:41, 9 March 2023DeSlRemoved empty comment in description
125758view10:39, 9 March 2023DeSlVertical layout enzymes
125757view10:38, 9 March 2023DeSlAdded missing ID for CYP7A1
125476view16:25, 17 February 2023SusanOntology Term : 'cholesterol biosynthetic pathway' added !
125475view20:15, 16 February 2023LLadeiraModified description
125474view20:12, 16 February 2023LLadeiraOntology Term : 'hepatocyte' added !
125473view20:10, 16 February 2023LLadeiraNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
24,25-DihydrolanosterolMetaboliteCHEBI:28113 (ChEBI)
24,25-epoxycholesterolMetaboliteCHEBI:41633 (ChEBI)
24S-hydroxycholesterolMetaboliteCHEBI:34310 (ChEBI)
25-hydroxycholesterolMetaboliteCHEBI:42977 (ChEBI)
27-hydroxycholesterolMetaboliteCHEBI:17703 (ChEBI)
4beta-hydroxycholesterolMetaboliteCHEBI:85778 (ChEBI)
7-DehydrocholesterolMetaboliteCHEBI:17759 (ChEBI)
7-DehydrodemosterolMetaboliteCHEBI:27910 (ChEBI)
7-oxocholesterolMetaboliteCHEBI:64294 (ChEBI)
7alpha-hydroxycholesterolMetaboliteCHEBI:17500 (ChEBI)
ABCA1GeneProductNM_005502 (RefSeq)
ABCG1GeneProductABCG1 (HGNC)
ACAT2GeneProduct39 (Entrez Gene)
ACOT1GeneProductQ86TX2 (Uniprot-TrEMBL)
ACOT2GeneProductNM_006821 (RefSeq)
ACSL1GeneProduct2180 (Entrez Gene)
ACSL3GeneProductNM_004457 (RefSeq)
ACSL4GeneProduct3571 (HGNC Accession number)
Acetoacetyl-CoAMetaboliteCHEBI:15345 (ChEBI)
Acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
BilePathwayGO:0006699 (GeneOntology) The chemical reactions and pathways resulting in the formation of bile acids, any of a group of steroid carboxylic acids occurring in bile.
CH25HProtein9023 (Entrez Gene)
CP7A1ProteinP22680 (Uniprot-TrEMBL)
CYP27A1ProteinCYP27A1 (HGNC)
CYP46A1ProteinNM_006668 (RefSeq)
CYP51A1ProteinQ16850 (Uniprot-TrEMBL)
Cell membranesPathwayGO:0044091 (GeneOntology) A cellular process that results in the biosynthesis of constituent macromolecules, assembly, and arrangement of constituent parts of a membrane.
CholestadienolMetaboliteCHEBI:145214 (ChEBI)
CholestenoneMetaboliteCHEBI:16175 (ChEBI)
CholesterolMetaboliteCHEBI:16113 (ChEBI)
DHCR24ProteinNM_014762 (RefSeq)
DHCR7Protein2860 (HGNC Accession number)
DMAPPMetaboliteCHEBI:57623 (ChEBI)
DesmosterolMetaboliteCHEBI:17737 (ChEBI)
Diepoxy-SqualeneMetaboliteCHEBI:138307 (ChEBI)
Dihydro-FF-MASMetaboliteCHEBI:78904 (ChEBI)
Dihydro-T-MASMetaboliteCHEBI:87044 (ChEBI)
EBPProtein10682 (Entrez Gene)
ELOVL2GeneProductQ9NXB9 (Uniprot-TrEMBL)
ELOVL3GeneProductQ9HB03 (Uniprot-TrEMBL)
ELOVL4GeneProductENSG00000118402 (Ensembl)
ELOVL5GeneProductNM_021814 (RefSeq)
FADS1GeneProduct3574 (HGNC Accession number)
FADS2GeneProductENSG00000134824 (Ensembl)
FAPPMetaboliteCHEBI:50277 (ChEBI)
FASNGeneProduct3594 (HGNC Accession number)
FDFT1ProteinFDFT1 (HGNC)
FDPSProteinNM_002004 (RefSeq)
FF-MASMetaboliteCHEBI:17813 (ChEBI)
Fatty Acid BiosynthesisPathwayWP4491 (WikiPathways) The chemical reactions and pathways resulting in the formation of a fatty acid, any of the aliphatic monocarboxylic acids that can be liberated by hydrolysis from naturally occurring fats and oils. Fatty acids are predominantly straight-chain acids of 4 to 24 carbon atoms, which may be saturated or unsaturated; branched fatty acids and hydroxy fatty acids also occur, and very long chain acids of over 30 carbons are found in waxes.
GGPS1Protein9453 (Entrez Gene)
GPPMetaboliteCHEBI:17211 (ChEBI)
HMG-CoAMetaboliteCHEBI:11814 (ChEBI)
HMGCRProteinENSG00000113161 (Ensembl)
HMGCS1GeneProductQ01581 (Uniprot-TrEMBL)
HMGCS2GeneProductP54868 (Uniprot-TrEMBL)
HSD17B7Protein51478 (Entrez Gene)
IDI1ProteinENSG00000067064 (Ensembl)
IDI2Protein91734 (Entrez Gene) IDI2 might catalize this reaction as well, however ther is no data supporting its occurrence in hepatocytes. https://www.proteinatlas.org/ENSG00000148377-IDI2/tissue/liver
Isopentenyl diphosphateMetaboliteCHEBI:16584 (ChEBI)
KetogenesisPathwayWP5175 (WikiPathways)
LBRProteinLBR (HGNC)
LDLR degradationPathwayGO:0032803 (GeneOntology) Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of low-density lipoprotein particle receptors.
LNSOLMetaboliteCHEBI:16521 (ChEBI)
LSSProteinLSS (HGNC)
LathosterolMetaboliteCHEBI:17168 (ChEBI)
LipoproteinsPathwayGO:0140306 (GeneOntology) The activity of recognizing mature outer membrane lipoproteins in the inner membrane and releasing from the inner membrane so that they can be transported across the periplasmic space to their target location, the outer membrane. This function exists in diderm bacteria, mediated by the LolCDE complex. The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues.
MSMO1ProteinNM_006745 (RefSeq)
MVDProteinMVD (HGNC)
MVKProteinNM_000431 (RefSeq)
MYLIPGeneProductNM_013262 (RefSeq)
Mevalonate-PMetaboliteCHEBI:25350 (ChEBI)
Mevalonate-PPMetaboliteCHEBI:25350 (ChEBI)
Mevalonic acidMetaboliteCHEBI:25351 (ChEBI)
Mg2+MetaboliteCHEBI:18420 (ChEBI)
NR1H2ProteinP55055 (Uniprot-TrEMBL)
NR1H3ProteinNM_001130101 (RefSeq)
NSDHLProtein50814 (Entrez Gene)
PLPP6ProteinPLPP6 (HGNC)
PMVKProteinPMVK (HGNC)
Presqualene diphosphateMetaboliteCHEBI:15442 (ChEBI)
Presqualene monophosphate MetaboliteCHEBI:134117 (ChEBI)
SC5DProtein6309 (Entrez Gene)
SCDGeneProductENSG00000099194 (Ensembl)
SQLEProtein11279 (HGNC Accession number)
SQNEMetaboliteCHEBI:15440 (ChEBI)
SQOXMetaboliteCHEBI:78662 (ChEBI)
SREBF1ProteinP36956 (Uniprot-TrEMBL)
SREBF2Protein11290 (HGNC Accession number)
Steroid synthesisPathwayGO:0006694 (GeneOntology) The chemical reactions and pathways resulting in the formation of steroids, compounds with a 1,2,cyclopentanoperhydrophenanthrene nucleus; includes de novo formation and steroid interconversion by modification.
Sterol EfluxPathwayGO:0035382 (GeneOntology) The process in which a sterol is transported across a membrane. Sterols are steroids with one or more hydroxyl groups and a hydrocarbon side-chain in the molecule.
T-MASMetaboliteCHEBI:18364 (ChEBI)
TM7SF2ProteinENSG00000149809 (Ensembl)
Vitamin D (Calciferol metabolism)PathwayGO:0042368 (GeneOntology) The chemical reactions and pathways resulting in the formation of vitamin D, any of a group of related, fat-soluble compounds that are derived from delta-5,7 steroids and play a central role in calcium metabolism. Specific forms of vitamin D include calciferol (ergocalciferol; vitamin D2) and cholecalciferol (calciol; vitamin D3).
ZymostenolMetaboliteCHEBI:16608 (ChEBI)
ZymosterolMetaboliteCHEBI:18252 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
24,25-DihydrolanosterolDihydro-FF-MASArrowWP4718 (WikiPathways)
7-DehydrodemosterolDesmosterolArrowWP4718 (WikiPathways)
7alpha-hydroxycholesterol7-oxocholesterolArrowWP4718 (WikiPathways)
ABCA1ABCA1mim-conversionWP4718 (WikiPathways)
ABCA1Sterol EfluxArrowWP4718 (WikiPathways)
ABCG1ABCG1mim-conversionWP4718 (WikiPathways)
ABCG1Sterol EfluxArrowWP4718 (WikiPathways)
ACAT2ACAT2mim-conversionWP4718 (WikiPathways)
ACOT1mim-conversionWP4718 (WikiPathways)
ACOT2ACOT2mim-conversionWP4718 (WikiPathways)
ACSL1mim-conversionWP4718 (WikiPathways)
ACSL3mim-conversionWP4718 (WikiPathways)
ACSL4mim-conversionWP4718 (WikiPathways)
Acetoacetyl-CoAHMG-CoAArrowWP4718 (WikiPathways)
Acetyl-CoAAcetoacetyl-CoAArrowWP4718 (WikiPathways)
Cholestadienol7-DehydrodemosterolArrowWP4718 (WikiPathways)
Cholesterol7alpha-hydroxycholesterolArrowWP4718 (WikiPathways)
CholesterolArrowWP4718 (WikiPathways)
DMAPPGPPArrowWP4718 (WikiPathways)
DesmosterolCholesterolArrowWP4718 (WikiPathways)
Diepoxy-Squalene24,25-epoxycholesterolmim-conversionWP4718 (WikiPathways)
Dihydro-FF-MASDihydro-T-MASArrowWP4718 (WikiPathways)
Dihydro-T-MASZymostenolmim-conversionWP4718 (WikiPathways)
ELOVL2mim-conversionWP4718 (WikiPathways)
ELOVL3mim-conversionWP4718 (WikiPathways)
ELOVL4mim-conversionWP4718 (WikiPathways)
ELOVL5mim-conversionWP4718 (WikiPathways)
FADS1mim-conversionWP4718 (WikiPathways)
FADS2mim-conversionWP4718 (WikiPathways)
FAPPPresqualene diphosphateArrowWP4718 (WikiPathways)
FASNFASNmim-conversionWP4718 (WikiPathways)
FF-MASDihydro-FF-MASArrowWP4718 (WikiPathways)
FF-MAST-MASArrowWP4718 (WikiPathways)
GPPFAPPArrowWP4718 (WikiPathways)
HMG-CoAMevalonic acidArrowWP4718 (WikiPathways)
HMGCS1HMGCS1mim-conversionWP4718 (WikiPathways)
HMGCS2HMGCS2mim-conversionWP4718 (WikiPathways)
Isopentenyl diphosphateDMAPPArrowWP4718 (WikiPathways)
LNSOLFF-MASArrowWP4718 (WikiPathways)
Lathosterol7-DehydrocholesterolArrowWP4718 (WikiPathways)
MYLIPLDLR degradationArrowWP4718 (WikiPathways)
MYLIPMYLIPmim-conversionWP4718 (WikiPathways)
Mevalonate-PMevalonate-PPArrowWP4718 (WikiPathways)
Mevalonate-PPIsopentenyl diphosphateArrowWP4718 (WikiPathways)
Mevalonic acidMevalonate-PArrowWP4718 (WikiPathways)
NR1H2NR1H2ArrowWP4718 (WikiPathways)
NR1H3NR1H3ArrowWP4718 (WikiPathways)
Presqualene diphosphateSQNEArrowWP4718 (WikiPathways)
SCDmim-conversionWP4718 (WikiPathways)
SQNESQOXArrowWP4718 (WikiPathways)
SQOXDiepoxy-SqualeneArrowWP4718 (WikiPathways)
SQOXLNSOLArrowWP4718 (WikiPathways)
SREBF1SREBF1ArrowWP4718 (WikiPathways)
SREBF2SREBF2ArrowWP4718 (WikiPathways)
T-MASZymosterolmim-conversionWP4718 (WikiPathways)
ZymostenolLathosterolArrowWP4718 (WikiPathways)
ZymosterolCholestadienolArrowWP4718 (WikiPathways)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5329"
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