Nuclear Receptors in Lipid Metabolism and Toxicity (Homo sapiens)

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Gene expressionXenobioticsDIETDIETCYP7A1RARGAcetyl CoASteroidsABCB1aIsoprenoidsRARAABCC27-DehydroCholesterolCYP2C9VDRABCB11NR1I2ABCB1CYP24A1CYP2B6abcg6CYP1A2CYP2E1CYP3A4CYP7A1OxysterolCYP4A11ABCA11,25-Dihydroxy-Vitamins D3ABCA1ABCB4NR1I3ABCD3ABCG1CYP27B1PPARGCYP2C9CYP7A1CYP3A4CYP2B6NR1H4Fatty AcidsLanosterolCYP4B1Retinoic acidCYP8B1CYP3A4CYP26A1ABCD2Bile AcidsCholesterolRARBABCC3ABCG5PPARDPPARANR1H3CYP2C9ABCA1


Nuclear receptors are transcription factors that are activated upon binding to its ligands. Initially, they had been classified as classic endocrine nuclear hormone receptors and orphan receptors. However, further studies have led to the identification of lipid ligands for some of these ‘adopted’ orphan receptors, which are responsible for lipid metabolism, storage or elimination. One of the characteristics of these receptors is that they act by forming heterodimers with retinoid X receptor (RXR). The receptors include peroxisome proliferators-Activated receptors (PPARs) for fatty acids, liver X receptor (LCR) for oxysterols, Farnesoid X receptors (FXR) for bile acids and steroid xenobiotic receptor/X receptor (SXR/PXR or Nsil2) for xenobiotics. Other orphan receptors also require RXR for its functions are vitamin D receptor (VDR) for vitamin D and retinoic acid receptor (RAR) for retinoid acids, although these receptors are not involved in lipid metabolism. Upon binding to various ligands, three classes of proteins are synthesized including lipid binding proteins, the ATP-binding cassette (ABC) transporters and cytochrome P450 member proteins which catalyzes lipid anabolism, metabolism and elimination. In addition to lipid metabolism, some members of the cytochrome P450 family genes are responsible for activation of procarcinogens, detoxification of environmental toxins and metabolism of drugs and xenobiotics. In particular, CAR, Nsil2 and recently identified VDR are important in up-regulation of these cytochromes. Of all the human cytochrome P450 genes, only a few CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 account for most toxicity effects, specifically CYP3A is responsible for clearing approximately half of the clinically prescribed drugs. For instance, acetaminophen, one of the most commonly used drug, is toxic in high doses due to the activation of CAR and the drug’s subsequentconversion to acetyl-p-benzoquinone imine (NAPQI) by CYP1A2, CYP2E1 and CYP3A.


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107139view14:22, 17 September 2019MaintBotChEBI identifier normalization
106730view13:21, 17 September 2019MaintBotHMDB identifier normalization
106665view21:26, 12 September 2019KhanspersModified description
105760view19:32, 15 August 2019KhanspersModified description
96301view18:20, 7 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
89331view09:59, 4 September 2016Mkutmonfix unconnected lines
78587view14:51, 7 January 2015MaintBotadded missing graphIds
78018view16:37, 11 November 2014EgonwAdded a few missing metabolite identifiers.
70027view01:54, 12 July 2013AlexanderPicoModified title
68978view17:42, 8 July 2013MaintBotUpdated to 2013 gpml schema
61677view21:32, 16 April 2013MaintBotremoved data source without identifer
59772view18:05, 7 March 2013EgonwConverted 'xenobiotics' to a DataNode and added the ChEBI id.
59771view17:56, 7 March 2013EgonwAdded two ChEBI ids for metabolite classes.
59184view18:51, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45336view20:19, 7 October 2011Khansperscleaned up description and removed old comment
45334view20:18, 7 October 2011KhanspersOntology Term : 'lipid metabolic pathway' added !
45143view01:11, 7 October 2011AlexanderPicoSpecify description
43564view23:09, 29 June 2011Samuel Sklarmir33 added
43563view22:54, 29 June 2011Samuel SklarPeriodical save, work in progress
41152view23:40, 1 March 2011MaintBotRemoved redundant pathway information and comments
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34436view18:16, 10 December 2009MaintBotAutomatic update of empty xrefs
32035view13:27, 14 August 2009MaintBotFixed group labels
21309view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:WP299]]: Moved to stable identifier
14008view17:20, 20 May 2008Thomasconnected lines
14006view17:13, 20 May 2008Thomasadded some metabolite annotations
13095view11:15, 17 May 2008MaintBotautomated metabolite conversion
8290view13:46, 7 January 2008MaintBot[[Pathway:Human:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:Homo sapiens:Nuclear receptors in lipid metabolism and toxicity]]: Renaming species
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External references


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NameTypeDatabase referenceComment
1,25-Dihydroxy-Vitamins D3Metabolite
7-DehydroCholesterolMetabolite434-16-2 (CAS)
ABCA1GeneProduct19 (Entrez Gene)
ABCB11GeneProduct8647 (Entrez Gene)
ABCB1GeneProduct5243 (Entrez Gene)
ABCB4GeneProduct5244 (Entrez Gene)
ABCC2GeneProduct1244 (Entrez Gene)
ABCC3GeneProduct8714 (Entrez Gene)
ABCD2GeneProduct225 (Entrez Gene)
ABCD3GeneProduct5825 (Entrez Gene)
ABCG1GeneProduct9619 (Entrez Gene)
ABCG5GeneProduct64240 (Entrez Gene)
Acetyl CoAMetabolite72-89-9 (CAS)
Bile AcidsMetabolite3098 (ChEBI)
CYP1A2GeneProduct1544 (Entrez Gene)
CYP24A1GeneProduct1591 (Entrez Gene)
CYP26A1GeneProduct1592 (Entrez Gene)
CYP27B1GeneProduct1594 (Entrez Gene)
CYP2B6GeneProduct1555 (Entrez Gene)
CYP2C9GeneProduct1559 (Entrez Gene)
CYP2E1GeneProduct1571 (Entrez Gene)
CYP3A4GeneProduct1576 (Entrez Gene)
CYP4A11GeneProduct1579 (Entrez Gene)
CYP4B1GeneProduct1580 (Entrez Gene)
CYP7A1GeneProduct1581 (Entrez Gene)
CYP8B1GeneProduct1582 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
Fatty AcidsMetabolite35366 (ChEBI)
IsoprenoidsMetabolite24913 (ChEBI)
LanosterolMetabolite6374 (ChEBI)
NR1H3GeneProduct10062 (Entrez Gene)
NR1H4GeneProduct9971 (Entrez Gene) Farnesoid X-activated receptor
NR1I2GeneProduct8856 (Entrez Gene)
NR1I3GeneProduct9970 (Entrez Gene)
PPARAGeneProduct5465 (Entrez Gene)
PPARDGeneProduct5467 (Entrez Gene)
PPARGGeneProduct5468 (Entrez Gene)
RARAGeneProduct5914 (Entrez Gene)
RARBGeneProduct5915 (Entrez Gene)
RARGGeneProduct5916 (Entrez Gene)
Retinoic acidMetaboliteHMDB01852 (HMDB)
VDRGeneProduct7421 (Entrez Gene)

Annotated Interactions

No annotated interactions
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