Cholesterol biosynthesis pathway in hepatocytes (WP5329)

Homo sapiens

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.


Luiz C. M. Ladeira , Susan Coort , Denise Slenter , Javier Millán Acosta , and Egon Willighagen


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Homo sapiens



Pathway Ontology

cholesterol biosynthetic pathway

Cell Type Ontology



Label Type Compact URI Comment
4beta-hydroxycholesterol Metabolite chebi:85778
7alpha-hydroxycholesterol Metabolite chebi:17500
24S-hydroxycholesterol Metabolite chebi:34310
25-hydroxycholesterol Metabolite chebi:42977
Presqualene monophosphate Metabolite chebi:134117
24,25-epoxycholesterol Metabolite chebi:41633
27-hydroxycholesterol Metabolite chebi:17703
Diepoxy-Squalene Metabolite chebi:138307
Isopentenyl diphosphate Metabolite chebi:16584
Presqualene diphosphate Metabolite chebi:15442
7-Dehydrocholesterol Metabolite chebi:17759
24,25-Dihydrolanosterol Metabolite chebi:28113
7-Dehydrodemosterol Metabolite chebi:27910
7-oxocholesterol Metabolite chebi:64294
Cholestenone Metabolite chebi:16175
Dihydro-FF-MAS Metabolite chebi:78904
Acetoacetyl-CoA Metabolite chebi:15345
Mevalonate-PP Metabolite chebi:25350
Dihydro-T-MAS Metabolite chebi:87044
Mevalonate-P Metabolite chebi:25350
T-MAS Metabolite chebi:18364
Zymosterol Metabolite chebi:18252
Mevalonic acid Metabolite chebi:25351
Zymostenol Metabolite chebi:16608
FF-MAS Metabolite chebi:17813
Cholestadienol Metabolite chebi:145214
Desmosterol Metabolite chebi:17737
DMAPP Metabolite chebi:57623
Acetyl-CoA Metabolite chebi:15351
HMG-CoA Metabolite chebi:11814
GPP Metabolite chebi:17211
FAPP Metabolite chebi:50277
SQNE Metabolite chebi:15440
SQOX Metabolite chebi:78662
LNSOL Metabolite chebi:16521
Cholesterol Metabolite chebi:16113
Lathosterol Metabolite chebi:17168
Mg2+ Metabolite chebi:18420
ACAT2 GeneProduct ncbigene:39
HMGCS1 GeneProduct uniprot:Q01581
HMGCS2 GeneProduct uniprot:P54868
FASN GeneProduct hgnc:3594
ACSL1 GeneProduct ncbigene:2180
ACSL3 GeneProduct refseq:NM_004457
ACSL4 GeneProduct hgnc:3571
ELOVL2 GeneProduct uniprot:Q9NXB9
ELOVL3 GeneProduct uniprot:Q9HB03
ELOVL4 GeneProduct ensembl:ENSG00000118402
ELOVL5 GeneProduct refseq:NM_021814
FADS1 GeneProduct hgnc:3574
FADS2 GeneProduct ensembl:ENSG00000134824
SCD GeneProduct ensembl:ENSG00000099194
ACOT1 GeneProduct uniprot:Q86TX2
ACOT2 GeneProduct refseq:NM_006821
ABCA1 GeneProduct refseq:NM_005502
ABCG1 GeneProduct hgnc.symbol:ABCG1
MYLIP GeneProduct refseq:NM_013262
GGPS1 Protein ncbigene:9453
SREBF2 Protein hgnc:11290
SREBF2 Protein hgnc:11290
CP7A1 Protein uniprot:P22680
FDPS Protein refseq:NM_002004
FDFT1 Protein hgnc.symbol:FDFT1
SQLE Protein hgnc:11279
LSS Protein hgnc.symbol:LSS
PMVK Protein hgnc.symbol:PMVK
CYP51A1 Protein uniprot:Q16850
TM7SF2 Protein ensembl:ENSG00000149809
LBR Protein hgnc.symbol:LBR
MSMO1 Protein refseq:NM_006745
NSDHL Protein ncbigene:50814
MVK Protein refseq:NM_000431
HSD17B7 Protein ncbigene:51478
EBP Protein ncbigene:10682
NR1H3 Protein refseq:NM_001130101
DHCR7 Protein hgnc:2860
DHCR24 Protein refseq:NM_014762
SC5D Protein ncbigene:6309
ACAT2 Protein ncbigene:39
NR1H3 Protein refseq:NM_001130101
PLPP6 Protein hgnc.symbol:PLPP6
HMGCR Protein ensembl:ENSG00000113161
LBR Protein hgnc.symbol:LBR
MSMO1 Protein refseq:NM_006745
NSDHL Protein ncbigene:50814
HMGCS1 Protein uniprot:Q01581 -- 'Cytosolic HMGCS1 synthesises HMGCoA for cholesterol synthesis, whereas the related mitochondrial HMGCS2 produces HMG-CoA for ketogenesis and stimulates fatty acid oxidation.' DOI: 10.1016/B978-0-12-824048-9.00005-5 -- Localized to the Nucleoplasm, Cytosol In addition localized to the Plasma membrane
HSD17B7 Protein ncbigene:51478
TM7SF2 Protein ensembl:ENSG00000149809
IDI2 Protein ncbigene:91734 IDI2 might catalize this reaction as well, however ther is no data supporting its occurrence in hepatocytes.
MVD Protein hgnc.symbol:MVD
CYP46A1 Protein refseq:NM_006668
CYP27A1 Protein hgnc.symbol:CYP27A1
CH25H Protein ncbigene:9023
NR1H2 Protein uniprot:P55055
IDI1 Protein ensembl:ENSG00000067064
NR1H2 Protein uniprot:P55055
SREBF1 Protein uniprot:P36956
SREBF1 Protein uniprot:P36956


  1. Cholesterol biosynthesis and metabolism. Russell DW. Cardiovasc Drugs Ther. 1992 Apr;6(2):103–10. PubMed Europe PMC Scholia
  2. Regulation of cholesterol biosynthesis. Rudney H, Sexton RC. Annu Rev Nutr. 1986;6:245–72. PubMed Europe PMC Scholia
  3. Membrane-bound enzymes of cholesterol synthesis from lanosterol. Gaylor JL. Biochem Biophys Res Commun. 2002 Apr 19;292(5):1139–46. PubMed Europe PMC Scholia
  4. Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Herman GE. Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R75-88. PubMed Europe PMC Scholia
  5. Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol. Song BL, Javitt NB, DeBose-Boyd RA. Cell Metab. 2005 Mar;1(3):179–89. PubMed Europe PMC Scholia