Nuclear receptors in lipid metabolism and toxicity (Mus musculus)

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XenobioticsGene expressionDIETDIETNr1i2Nr1h4Abcg1PparaAcetyl-CoACholesterolAbcb11Cyp1a2Abcb1aCyp24a1abcg6Abca1Abcg5Abcc2Abcd2SteroidsRetinoic acidOxysterolCYP4A11Cyp8b1CYP3A4Abcd3Nr1h3Abcc3CYP2C9Cyp7a1Fatty AcidsRaraPpardCyp7a1RargLanosterol7-DehydrocholesterolCyp7a1IsoprenoidsNr1i3CYP3A4Cyp27b11,25-Dihydroxyvitamin D3sCyp4b1RarbCYP2C9Bile AcidsPpargCYP2C9Abcb1aCyp2b10Abca1Cyp2b10CYP3A4VdrCyp26a1Abcb4Cyp2e1Abca1


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 drugs subsequent conversion to acetyl-p-benzoquinone imine (NAPQI) by CYP1A2, CYP2E1 and CYP3A.


GenMAPP remarks 
Converted to human by
This pathway was inferred from Homo sapiens pathway WP299(r21309) with a 76% conversion rate.

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107205view14:29, 17 September 2019MaintBotChEBI identifier normalization
106893view13:36, 17 September 2019MaintBotHMDB identifier normalization
96445view08:34, 15 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
89979view18:46, 6 October 2016Mkutmonfix unconnected lines
89870view12:38, 6 October 2016MkutmonModified description
69992view22:18, 11 July 2013MaintBotupdated to 2013 schema
67539view11:23, 26 June 2013DdiglesOntology Term : 'lipid metabolic pathway' added !
47744view19:17, 5 April 2012Thomasfixed wrongly annotated gene
41254view00:20, 2 March 2011MaintBotRemoved redundant pathway information and comments
35675view22:48, 12 February 2010KhanspersDescription
35674view22:47, 12 February 2010KhanspersModified description
34373view22:43, 9 December 2009MaintBotAutomatic update of empty xrefs
32990view18:39, 30 September 2009MaintBotAdded xrefs
32095view13:43, 14 August 2009MaintBotFixed group labels
30823view23:59, 29 July 2009MaintBotConverted from Homo sapiens
21588view11:32, 14 November 2008MaintBot[[Pathway:Mus musculus:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:WP431]]: Moved to stable identifier
8292view13:46, 7 January 2008MaintBot[[Pathway:Mouse:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:Mus musculus:Nuclear receptors in lipid metabolism and toxicity]]: Renaming species
7766view16:16, 18 December 2007MaintBotfixed category names
7382view12:42, 4 November 2007MaintBotAdded categories to GPML
6480view22:19, 22 May 2007S.Burelgpml file for [[Mouse:Nuclear_receptors_in_lipid_metabolism_and_toxicity]]

External references


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NameTypeDatabase referenceComment
1,25-Dihydroxyvitamin D3sMetaboliteHMDB0000969 (HMDB)
7-DehydrocholesterolMetaboliteHMDB0000032 (HMDB)
Abca1GeneProduct11303 (Entrez Gene)
Abcb11GeneProduct27413 (Entrez Gene)
Abcb1aGeneProduct18671 (Entrez Gene)
Abcb4GeneProduct18670 (Entrez Gene)
Abcc2GeneProduct12780 (Entrez Gene)
Abcc3GeneProduct76408 (Entrez Gene)
Abcd2GeneProduct26874 (Entrez Gene)
Abcd3GeneProduct19299 (Entrez Gene)
Abcg1GeneProduct11307 (Entrez Gene)
Abcg5GeneProduct27409 (Entrez Gene)
Acetyl-CoAMetaboliteHMDB0001206 (HMDB)
Bile AcidsMetabolite3098 (ChEBI)
CholesterolMetaboliteHMDB0000067 (HMDB)
Cyp1a2GeneProduct13077 (Entrez Gene)
Cyp24a1GeneProduct13081 (Entrez Gene)
Cyp26a1GeneProduct13082 (Entrez Gene)
Cyp27b1GeneProduct13115 (Entrez Gene)
Cyp2b10GeneProduct13088 (Entrez Gene)
Cyp2e1GeneProduct13106 (Entrez Gene)
Cyp4b1GeneProduct13120 (Entrez Gene)
Cyp7a1GeneProduct13122 (Entrez Gene)
Cyp8b1GeneProduct13124 (Entrez Gene)
Fatty AcidsMetabolite35366 (ChEBI)
IsoprenoidsMetabolite24913 (ChEBI)
LanosterolMetaboliteCHEBI:16521 (ChEBI)
Nr1h3GeneProduct22259 (Entrez Gene)
Nr1h4GeneProduct20186 (Entrez Gene) Farnesoid X-activated receptor
Nr1i2GeneProduct18171 (Entrez Gene)
Nr1i3GeneProduct12355 (Entrez Gene)
PparaGeneProduct19013 (Entrez Gene)
PpardGeneProduct19015 (Entrez Gene)
PpargGeneProduct19016 (Entrez Gene)
RaraGeneProduct19401 (Entrez Gene)
RarbGeneProduct218772 (Entrez Gene)
RargGeneProduct19411 (Entrez Gene)
Retinoic acidMetaboliteHMDB0001852 (HMDB)
VdrGeneProduct22337 (Entrez Gene)

Annotated Interactions

No annotated interactions
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