Nuclear receptors in lipid metabolism and toxicity (Canis familiaris)

From WikiPathways

Jump to: navigation, search
DIETDIETXenobioticsGene expressionLanosterolBile AcidsCYP2C9CYP7A1PPARDABCD3MIR33ACYP7A1ABCC3VDRCYP24A1CYP2E1MIR33BNR1H4ABCD2Acetyl CoA7-DehydroCholesterolABCA1LOC485619CYP26A1CYP2B6CYP2C9CYP4A11RARARetinoic acidCYP2B6IsoprenoidsCYP27B1CholesterolCYP3A4CYP7A1Fatty AcidsABCG5abcg6CYP3A4ABCB1ABCB4NR1I2CYP2C9ABCC21,25-Dihydroxy-Vitamins D3ABCG1CYP4B1SteroidsABCA1RARGNR1H3ABCA1CYP1A2PPARAABCB11PPARGOxysterolNR1I3RARBABCB1aCYP3A4MIR33AMIR33BMIR33AMIR33B


Description

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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP299(r45336) with a 70% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

No bibliography


History

View all...
CompareRevisionActionTimeUserComment
107084view14:17, 17 September 2019MaintBotChEBI identifier normalization
106033view11:55, 16 August 2019MaintBotHMDB identifier normalization
96375view16:48, 10 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
78444view10:27, 7 January 2015MaintBotadded missing graphIds
71472view19:17, 17 October 2013MaintBotAutomated update of data sources
67536view11:22, 26 June 2013DdiglesOntology Term : 'lipid metabolic pathway' added !
62304view11:09, 27 April 2013EgonwAdded a ChEBI identifier for 'steroid'.
62301view11:07, 27 April 2013EgonwConverted 'xenobiotics' to a DataNode and added the ChEBI id.
48156view18:51, 9 May 2012MaintBotUpdating from human to fix xrefs
40713view21:52, 1 March 2011MaintBotRemoved redundant pathway information and comments
35682view22:52, 12 February 2010KhanspersDescription
35681view22:52, 12 February 2010KhanspersModified description
33992view18:35, 9 December 2009MaintBotAutomatic update of empty xrefs
31726view11:56, 14 August 2009MaintBotFixed group labels
30668view22:39, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,25-Dihydroxy-Vitamins D3Metabolite
7-DehydroCholesterolMetabolite434-16-2 (CAS)
ABCA1GeneProduct481651 (Entrez Gene)
ABCB11GeneProduct488390 (Entrez Gene)
ABCB1GeneProduct403879 (Entrez Gene)
ABCB1aGeneProduct
ABCB4GeneProduct482284 (Entrez Gene)
ABCC2GeneProduct403632 (Entrez Gene)
ABCC3GeneProduct491084 (Entrez Gene)
ABCD2GeneProduct477643 (Entrez Gene)
ABCD3GeneProduct479939 (Entrez Gene)
ABCG1GeneProduct487777 (Entrez Gene)
ABCG5GeneProduct481354 (Entrez Gene)
Acetyl CoAMetabolite72-89-9 (CAS)
Bile AcidsMetaboliteCHEBI:3098 (ChEBI)
CYP1A2GeneProduct494010 (Entrez Gene)
CYP24A1GeneProduct485935 (Entrez Gene)
CYP26A1GeneProduct486804 (Entrez Gene)
CYP27B1GeneProduct481133 (Entrez Gene)
CYP2B6GeneProduct474177 (Entrez Gene)
CYP2C9GeneProduct
CYP2E1GeneProduct415128 (Entrez Gene)
CYP3A4GeneProduct
CYP4A11GeneProduct
CYP4B1GeneProduct608452 (Entrez Gene)
CYP7A1GeneProduct486962 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
Fatty AcidsMetaboliteCHEBI:35366 (ChEBI)
IsoprenoidsMetaboliteCHEBI:24913 (ChEBI)
LOC485619GeneProduct485619 (Entrez Gene)
LanosterolMetaboliteCHEBI:16521 (ChEBI)
MIR33AGeneProduct
MIR33BGeneProduct
NR1H3GeneProduct483625 (Entrez Gene)
NR1H4GeneProduct612928 (Entrez Gene) Farnesoid X-activated receptor
NR1I2GeneProduct403482 (Entrez Gene)
NR1I3GeneProduct488653 (Entrez Gene)
OxysterolMetabolite
PPARAGeneProduct403654 (Entrez Gene)
PPARDGeneProduct481756 (Entrez Gene)
PPARGGeneProduct403606 (Entrez Gene)
RARAGeneProduct480526 (Entrez Gene)
RARBGeneProduct477045 (Entrez Gene)
RARGGeneProduct486508 (Entrez Gene)
Retinoic acidMetaboliteHMDB0001852 (HMDB)
SteroidsMetabolite
VDRGeneProduct486588 (Entrez Gene)
XenobioticsMetaboliteCHEBI:35703 (ChEBI)
abcg6GeneProduct

Annotated Interactions

No annotated interactions
Personal tools