Nuclear receptors in lipid metabolism and toxicity (Gallus gallus)

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DIETXenobioticsDIETGene expressionPPARDAcetyl CoAABCB11CYP4B1CYP26A1ABCB1AABCD3ABCA1CYP27B1CYP24A1CYP1A2VDRABCA1PPARGIsoprenoidsABCB4CYP3A80OxysterolNR1I2ABCA1CYP2B61,25-Dihydroxy-Vitamins D3CYP2C9CYP8BLanosterolCYP3A80CYP7A1ABCD2Fatty AcidsCYP3A80CYP2C9CholesterolABCB1CYP4B1SteroidsNR1H4CYP7A1RARBABCG5CYP2C9RARGBile AcidsRARAPPARAABCC2Retinoic acidCYP2E1CYP7A1NR1I3ABCG1NR1H3abcg6CYP2B67-DehydroCholesterolABCC3


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 drug’s subsequentconversion to acetyl-p-benzoquinone imine (NAPQI) by CYP1A2, CYP2E1 and CYP3A.

Comments

GenMAPP remarks 
Converted to human by GenMAPP.org
HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP299(r21309) with a 57% conversion rate.

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History

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CompareRevisionActionTimeUserComment
109452view10:21, 18 March 2020L DupuisDeleted unconnected line and converted interaction line in legend to graphical line
107105view14:18, 17 September 2019MaintBotChEBI identifier normalization
106108view12:01, 16 August 2019MaintBotHMDB identifier normalization
96343view09:27, 9 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
89869view12:38, 6 October 2016MkutmonModified description
89868view12:37, 6 October 2016MkutmonModified description
89867view12:35, 6 October 2016MkutmonModified description
74225view15:10, 8 April 2014EgonwRemoved a data source where no ID was given.
72374view13:03, 13 November 2013EgonwRemoved a few data sources where no identifier was given.
69991view22:17, 11 July 2013MaintBotupdated to 2013 schema
67540view11:23, 26 June 2013DdiglesOntology Term : 'lipid metabolic pathway' added !
47791view16:29, 6 April 2012Khanspersupdated xref
41023view22:57, 1 March 2011MaintBotRemoved redundant pathway information and comments
35690view22:58, 12 February 2010KhanspersDescription
35688view22:57, 12 February 2010KhanspersModified description
33944view18:15, 9 December 2009MaintBotAutomatic update of empty xrefs
33440view14:57, 30 November 2009MaintBotRemoved group label
30324view20:44, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1,25-Dihydroxy-Vitamins D3Metabolite
7-DehydroCholesterolMetabolite
ABCA1GeneProduct373945 (Entrez Gene)
ABCB11GeneProduct424170 (Entrez Gene)
ABCB1GeneProduct420534 (Entrez Gene)
ABCB1AGeneProduct
ABCB4GeneProduct
ABCC2GeneProduct423828 (Entrez Gene)
ABCC3GeneProduct422099 (Entrez Gene)
ABCD2GeneProduct417694 (Entrez Gene)
ABCD3GeneProduct424487 (Entrez Gene)
ABCG1GeneProduct418533 (Entrez Gene)
ABCG5GeneProduct421401 (Entrez Gene)
Acetyl CoAMetabolite
Bile AcidsMetabolite3098 (ChEBI)
CYP1A2GeneProduct414856 (Entrez Gene)
CYP24A1GeneProduct395827 (Entrez Gene)
CYP26A1GeneProduct408183 (Entrez Gene)
CYP27B1GeneProduct
CYP2B6GeneProduct
CYP2C9GeneProduct
CYP2E1GeneProduct
CYP3A80GeneProduct416477 (Entrez Gene)
CYP4B1GeneProduct424618 (Entrez Gene)
CYP7A1GeneProduct414834 (Entrez Gene)
CYP8BGeneProduct425055 (Entrez Gene)
CholesterolMetabolite
Fatty AcidsMetabolite35366 (ChEBI)
IsoprenoidsMetabolite24913 (ChEBI)
LanosterolMetabolite6374 (ChEBI)
NR1H3GeneProduct395221 (Entrez Gene)
NR1H4GeneProduct373902 (Entrez Gene) Farnesoid X-activated receptor
NR1I2GeneProduct
NR1I3GeneProduct395439 (Entrez Gene)
OxysterolMetabolite
PPARAGeneProduct374120 (Entrez Gene)
PPARDGeneProduct395479 (Entrez Gene)
PPARGGeneProduct373928 (Entrez Gene)
RARAGeneProduct395213 (Entrez Gene)
RARBGeneProduct396266 (Entrez Gene)
RARGGeneProduct
Retinoic acidMetaboliteHMDB01852 (HMDB)
SteroidsMetabolite
VDRGeneProduct395988 (Entrez Gene)
abcg6GeneProduct

Annotated Interactions

No annotated interactions
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