Nuclear receptors in lipid metabolism and toxicity (Rattus norvegicus)

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Gene expressionXenobioticsDIETDIETNr1i2Nr1h4Abcg1PparaAcetyl CoACholesterolABCB11Cyp1a2Abcb1aCyp24a1abcg6Abca1Abcg5ABCC2Abcd2SteroidsRetinoic acidOxysterolCYP4A11Cyp8b1CYP3A4Abcd3Nr1h3Abcc3Cyp2cCyp7a1Fatty AcidsRaraPpardCyp7a1RargLanosterol7-DehydrocholesterolCyp7a1IsoprenoidsNr1i3CYP3A4CYP27B1CalcitriolCyp4b1RARBCyp2cBile AcidsPpargCyp2cAbcb1Cyp2b2Abca1Cyp2b2CYP3A4VdrCyp26a1Abcb4Cyp2e1Abca1


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 74% conversion rate.

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107234view14:33, 17 September 2019MaintBotChEBI identifier normalization
106964view13:42, 17 September 2019MaintBotHMDB identifier normalization
89871view12:38, 6 October 2016MkutmonModified description
79807view16:33, 16 April 2015Mkutmonchanged legend to use graphical lines
71834view19:39, 18 October 2013MaintBotremoved data source from nodes without identifier
69990view22:15, 11 July 2013MaintBotupdated to 2013 schema
67538view11:22, 26 June 2013DdiglesOntology Term : 'lipid metabolic pathway' added !
60550view14:08, 21 March 2013Cizarannotated Calcitriol
60488view15:19, 20 March 2013CizarSpecify description
60487view15:09, 20 March 2013Cizarannotated 7-Dehydrocholesterol
60206view15:52, 14 March 2013SusanSpecify description
47780view05:49, 6 April 2012Khanspersupdated xref
41773view02:42, 2 March 2011MaintBotRemoved redundant pathway information and comments
35697view23:04, 12 February 2010KhanspersDescription
35696view23:03, 12 February 2010KhanspersModified description
34140view19:32, 9 December 2009MaintBotAutomatic update of empty xrefs
31965view13:06, 14 August 2009MaintBotFixed group labels
30928view00:36, 30 July 2009MaintBotConverted from Homo sapiens
20975view11:30, 14 November 2008MaintBot[[Pathway:Rattus norvegicus:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:WP139]]: Moved to stable identifier
8294view13:46, 7 January 2008MaintBot[[Pathway:Rat:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:Rattus norvegicus:Nuclear receptors in lipid metabolism and toxicity]]: Renaming species
7767view16:16, 18 December 2007MaintBotfixed category names
7383view12:42, 4 November 2007MaintBotAdded categories to GPML
6580view22:20, 22 May 2007S.Burelgpml file for [[Rat:Nuclear_receptors_in_lipid_metabolism_and_toxicity]]

External references


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NameTypeDatabase referenceComment
7-DehydrocholesterolMetaboliteHMDB0000032 (HMDB)
ABCB11GeneProduct83569 (Entrez Gene)
ABCC2GeneProduct25303 (Entrez Gene)
Abca1GeneProduct313210 (Entrez Gene)
Abcb1GeneProduct170913 (Entrez Gene)
Abcb1aGeneProduct170913 (Entrez Gene)
Abcb4GeneProduct24891 (Entrez Gene)
Abcc3GeneProduct140668 (Entrez Gene)
Abcd2GeneProduct84356 (Entrez Gene)
Abcd3GeneProduct25270 (Entrez Gene)
Abcg1GeneProduct85264 (Entrez Gene)
Abcg5GeneProduct114628 (Entrez Gene)
Acetyl CoAMetabolite
Bile AcidsMetaboliteCHEBI:3098 (ChEBI)
CYP27B1GeneProduct114700 (Entrez Gene)
CalcitriolMetaboliteHMDB0001903 (HMDB)
CholesterolMetaboliteHMDB0000067 (HMDB)
Cyp1a2GeneProduct24297 (Entrez Gene)
Cyp24a1GeneProduct25279 (Entrez Gene)
Cyp26a1GeneProduct154985 (Entrez Gene)
Cyp2b2GeneProduct361523 (Entrez Gene)
Cyp2cGeneProduct29277 (Entrez Gene)
Cyp2e1GeneProduct25086 (Entrez Gene)
Cyp4b1GeneProduct24307 (Entrez Gene)
Cyp7a1GeneProduct25428 (Entrez Gene)
Cyp8b1GeneProduct81924 (Entrez Gene)
Fatty AcidsMetaboliteCHEBI:35366 (ChEBI)
IsoprenoidsMetaboliteCHEBI:24913 (ChEBI)
LanosterolMetaboliteHMDB0001251 (HMDB)
Nr1h3GeneProduct58852 (Entrez Gene)
Nr1h4GeneProduct60351 (Entrez Gene) Farnesoid X-activated receptor
Nr1i2GeneProduct84385 (Entrez Gene)
Nr1i3GeneProduct65035 (Entrez Gene)
PparaGeneProduct25747 (Entrez Gene)
PpardGeneProduct25682 (Entrez Gene)
PpargGeneProduct25664 (Entrez Gene)
RARBGeneProduct24706 (Entrez Gene)
RaraGeneProduct24705 (Entrez Gene)
RargGeneProduct685072 (Entrez Gene)
Retinoic acidMetaboliteHMDB0001852 (HMDB)
VdrGeneProduct24873 (Entrez Gene)

Annotated Interactions

No annotated interactions
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