Cholesterol biosynthesis pathway in hepatocytes (WP5329)

Homo sapiens

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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.

Authors

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

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

cholesterol biosynthetic pathway

Cell Type Ontology

hepatocyte

Participants
Query Drugst.One

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 https://www.proteinatlas.org/ENSG00000112972-HMGCS1
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. https://www.proteinatlas.org/ENSG00000148377-IDI2/tissue/liver
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

References

  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