Statin inhibition of cholesterol production (WP430)

Statins inhibit endogenous cholesterol production by competitive inhibition of HMG-CoA reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol synthesis. This pathway delineates genes involved in statin pharmacogenomics, including genes involved in mediating the effects of statins on plasma lipoprotein metabolism. Sources: [https://www.pharmgkb.org/pathway/PA2031 PharmGKB] and [http://en.wikipedia.org/wiki/Statin Wikipedia] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP430 CPTAC Assay Portal].
last edited

Authors

Nsalomonis, AlexanderPico, MaintBot, Khanspers, Thomas, BruceConklin, Samuel Sklar, Egonw, Mkutmon, Evelo, Anwesha, DeSl, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Diseases

Annotations

Pathway Ontology: statin drug pathway

Disease Ontology: cardiovascular system disease

Cell Type Ontology: hepatocyte enterocyte

Participants

Label Type Compact Identifier
Cholesterol Metabolite cas:57-88-5
Cholesterol Metabolite cas:57-88-5
Squalene Metabolite hmdb:HMDB0000256
ABCA1 GeneProduct ncbigene:19
Acyl-CoA Metabolite hmdb:HMDB0003419
ABCG8 GeneProduct ncbigene:64241
APOA1 GeneProduct ncbigene:335
APOA4 GeneProduct ncbigene:337
ABCA1 GeneProduct ncbigene:19
APOC2 GeneProduct ncbigene:344
MIR33A GeneProduct ensembl:ENSG00000207932
APOC3 GeneProduct ncbigene:345
APOC1 GeneProduct ncbigene:341
Phospholipid Metabolite kegg.compound:C00865
APOA5 GeneProduct ncbigene:116519
DAG Metabolite kegg.compound:C00165
VLDL Metabolite chebi:39027
CYP7A1 GeneProduct ncbigene:1581
SCARB1 GeneProduct ncbigene:949
Cholesterol ester Metabolite kegg.compound:C02530
PLTP GeneProduct ncbigene:5360
ABCG5 GeneProduct ncbigene:64240
APOA2 GeneProduct ncbigene:336
Statin Metabolite chebi:35664
HMG-CoA Metabolite hmdb:HMDB0001375
LCAT GeneProduct ncbigene:3931
LDLR GeneProduct ncbigene:3949
APOB GeneProduct ncbigene:338
IDL Metabolite chebi:132933
Lipoproteins Metabolite chebi:6495
Cholesterol Metabolite cas:57-88-5
DGAT1 GeneProduct ncbigene:8694
LPL GeneProduct ncbigene:4023
MIR33B GeneProduct ensembl:ENSG00000207839
Mevalonate Metabolite chebi:25350
HDL Metabolite chebi:47775
SQLE GeneProduct ncbigene:6713
LIPC GeneProduct ncbigene:3990
Fatty acid Metabolite kegg.compound:C00162
SOAT1 GeneProduct ncbigene:6646
APOE GeneProduct ncbigene:348
Mevalonate armin more detail Pathway wikipathways:WP4190
Cholic Acid Metabolite cas:81-25-4
Cholesterol Metabolite cas:57-88-5
LRP1 GeneProduct ncbigene:4035
FDFT1 GeneProduct ncbigene:2222
LDL Metabolite chebi:47774
Acyl-CoA synthetase Protein ncbigene:84532
CETP GeneProduct ncbigene:1071
HMGCR GeneProduct ncbigene:3156
Triglyceride Metabolite kegg.compound:C00422
Cholesterol Metabolite cas:57-88-5
Triglyceride Metabolite kegg.compound:C00422
Phospholipid Metabolite kegg.compound:C00865
Cholesterol ester Metabolite kegg.compound:C02530
MTTP Protein ncbigene:4547
PDIA2 Protein ncbigene:64714

References

  1. Wetterau JR, Lin MC, Jamil H. Microsomal triglyceride transfer protein. Biochim Biophys Acta. 1997 Apr 1;1345(2):136–50. PubMed Europe PMC Scholia
  2. Chen H, Ikeda U, Shimpo M, Shimada K. Direct effects of statins on cells primarily involved in atherosclerosis. Hypertens Res. 2000 Mar;23(2):187–92. PubMed Europe PMC Scholia