Statin inhibition of cholesterol production (Homo sapiens)

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12EnterocytePeripheral tissuesActivationLiver cellPlasmaLDLCETPVLDLMTTPCholesterol esterABCG5SQLEABCG8MevalonateLIPCSCARB1APOA5LDLRAcetyl-CoATriglyceridePhospholipidAcyl-CoA synthetaseHDLAPOC1APOA1SOAT1APOA2PDIA2APOC2CholesterolLRP1MIR33BDAGAPOA4LPLAPOBSqualeneAPOECholesterolABCA1CholesterolLipoproteinsCholesterolABCA1Cholic AcidCYP7A1Acyl-CoAPLTPAPOC3StatinHMGCRIDLFDFT1DGAT1LCATMIR33AFatty acidInhibitionTransportCatalysisCholesterolTriglyceridePhospholipidCholesterol ester


Description

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: PharmGKB and Wikipedia

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Bibliography

  1. Chen H, Ikeda U, Shimpo M, Shimada K; ''Direct effects of statins on cells primarily involved in atherosclerosis.''; Hypertens Res, 2000 PubMed Europe PMC Scholia
  2. Wetterau JR, Lin MC, Jamil H; ''Microsomal triglyceride transfer protein.''; Biochim Biophys Acta, 1997 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
135479view04:59, 16 September 2024EgonwReplaced the formyl-CoA with the acyl-CoA identifier (matching the label)
135277view02:19, 11 August 2024EweitzEconomize layout, increase font size
122069view15:08, 9 March 2022DeSlUpdated translocation of LDL, IDL and HDL
120252view11:04, 21 November 2021EgonwMade a pathway clickable and typed two interactions as mim-translocation
119069view20:06, 14 June 2021KhanspersOntology Term : 'enterocyte' added !
116309view11:02, 29 April 2021EweitzModified title
108375view21:00, 13 December 2019EgonwUse the identifier of the particle, not of the cholesterol in it.
107641view17:54, 24 October 2019KhanspersModified title
106797view13:27, 17 September 2019MaintBotHMDB identifier normalization
105822view23:03, 15 August 2019KhanspersModified description
102293view19:17, 17 December 2018KhanspersModified description
102292view19:14, 17 December 2018KhanspersModified description
101737view12:40, 2 November 2018DeSlReverted to version '12:39, 2 November 2018' by DeSl
101736view12:40, 2 November 2018DeSlModified description
101735view12:39, 2 November 2018DeSlReverted to version '12:38, 2 November 2018' by DeSl
101734view12:38, 2 November 2018DeSlModified description
101733view12:38, 2 November 2018DeSlReverted to version '12:32, 2 November 2018' by DeSl
101732view12:38, 2 November 2018DeSlModified description
101727view12:32, 2 November 2018DeSlCHanged mim-conversion to arrow, when reaction contains multiple steps.
101726view12:29, 2 November 2018DeSlAdded PW link
96008view09:48, 15 February 2018DeSlRemoved "last modified" item
96007view09:46, 15 February 2018DeSlChanged MIM conversion between receptors(captured with gene IDs) and metabolite (cholesterol); should be translocation I believe. Same goes for LDL/IDL/HDL to these receptors (which where MIMbinding?!); this should be transport I believe (I changed these
95223view18:24, 26 November 2017DeSlRemoved licence number
95166view19:18, 19 November 2017Mkutmonfix identifiers for LDL, IDL, VLDL, HDL
90508view23:34, 19 November 2016AlexanderPicoIndicated multi-step reactions with dashed lines
85127view22:07, 18 April 2016AlexanderPicoQuick edit to datanode annotation or property
82344view22:57, 25 September 2015Khansperscorrected transport mechanisms
82251view22:59, 16 September 2015Khansperschanged Acetyl-CoA to HMG-CoA
82235view19:11, 16 September 2015Khansperscompleted transport events, connected receptors
78268view15:34, 19 December 2014AnweshaChanged line style
71273view22:20, 16 October 2013MaintBotAutomated update of data sources
69841view15:36, 11 July 2013EveloOntology Term : 'cardiovascular system disease' added !
68390view20:59, 4 July 2013Mkutmonreplaced interactions in legend with graphical lines
67910view23:17, 27 June 2013AlexanderPicoAdded ref for MTP:PDI complex
64356view05:43, 24 May 2013EgonwAdded missing metabolite identifiers.
59209view19:50, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45117view23:22, 6 October 2011KhanspersOntology Term : 'hepatocyte' added !
45116view23:20, 6 October 2011KhanspersOntology Term : 'statin drug pathway' added !
45115view23:20, 6 October 2011KhanspersOntology Term : 'CL:0000679' removed !
43561view21:13, 29 June 2011Samuel Sklarmir33 added
41203view23:44, 1 March 2011MaintBotRemoved redundant pathway information and comments
40175view21:38, 14 February 2011AlexanderPicoadded legend
40174view21:34, 14 February 2011AlexanderPicoModified description
39393view02:43, 20 November 2010AlexanderPicoSpecify description
39392view02:35, 20 November 2010AlexanderPicoupdated cells
38114view23:59, 12 August 2010AlexanderPico
38074view04:30, 9 August 2010AlexanderPicoliver cell
38073view04:26, 9 August 2010AlexanderPico
38072view04:25, 9 August 2010AlexanderPicooverhaul
37434view23:17, 2 June 2010NsalomonisSpecify description

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABCA1GeneProduct19 (Entrez Gene)
ABCG5GeneProduct64240 (Entrez Gene)
ABCG8GeneProduct64241 (Entrez Gene)
APOA1GeneProduct335 (Entrez Gene)
APOA2GeneProduct336 (Entrez Gene)
APOA4GeneProduct337 (Entrez Gene)
APOA5GeneProduct116519 (Entrez Gene)
APOBGeneProduct338 (Entrez Gene)
APOC1GeneProduct341 (Entrez Gene)
APOC2GeneProduct344 (Entrez Gene)
APOC3GeneProduct345 (Entrez Gene)
APOEGeneProduct348 (Entrez Gene)
Acetyl-CoAMetaboliteHMDB01206 (HMDB)
Acyl-CoA synthetaseProtein84532 (Entrez Gene)
Acyl-CoAMetaboliteHMDB03419 (HMDB)
CETPGeneProduct1071 (Entrez Gene)
CYP7A1GeneProduct1581 (Entrez Gene)
Cholesterol esterMetaboliteC02530 (KEGG Compound)
CholesterolMetabolite57-88-5 (CAS)
Cholic AcidMetabolite81-25-4 (CAS)
DAGMetaboliteC00165 (KEGG Compound)
DGAT1GeneProduct8694 (Entrez Gene)
FDFT1GeneProduct2222 (Entrez Gene)
Fatty acidMetaboliteC00162 (KEGG Compound)
HDLMetaboliteC01834 (KEGG Compound)
HMGCRGeneProduct3156 (Entrez Gene)
IDLMetaboliteC01834 (KEGG Compound)
LCATGeneProduct3931 (Entrez Gene)
LDLMetaboliteC01834 (KEGG Compound)
LDLRGeneProduct3949 (Entrez Gene)
LIPCGeneProduct3990 (Entrez Gene)
LPLGeneProduct4023 (Entrez Gene)
LRP1GeneProduct4035 (Entrez Gene)
LipoproteinsMetaboliteCHEBI:6495 (ChEBI)
MIR33AGeneProductENSG00000207932 (Ensembl)
MIR33BGeneProductENSG00000207839 (Ensembl)
MTTPProtein4547 (Entrez Gene)
MevalonateMetaboliteCHEBI:25350 (ChEBI)
PDIA2Protein64714 (Entrez Gene)
PLTPGeneProduct5360 (Entrez Gene)
PhospholipidMetaboliteC00865 (KEGG Compound)
SCARB1GeneProduct949 (Entrez Gene)
SOAT1GeneProduct6646 (Entrez Gene)
SQLEGeneProduct6713 (Entrez Gene)
SqualeneMetaboliteHMDB00256 (HMDB)
StatinMetaboliteCHEBI:35664 (ChEBI)
TriglycerideMetaboliteC00422 (KEGG Compound)
VLDLMetaboliteC01834 (KEGG Compound)

Annotated Interactions

No annotated interactions

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