Nuclear Receptors in Lipid Metabolism and Toxicity (Bos taurus)

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Gene expressionDIETXenobioticsDIETLanosterolCYP3A4Fatty AcidsAcetyl CoARetinoic acidBile AcidsABCC3RARGNR1I3NR1I2CYP3A4OxysterolABCB1Cholesterol1,25-Dihydroxy-Vitamins D3CYP2E1ABCC2CYP26A1ABCA1NR1H3CYP2C9bta-mir-33aCYP4B1ABCD2RARBRARAbta-mir-33bCYP2C9ABCB1aabcg6CYP3A4CYP7A1ABCA1CYP2C9CYP1A2SteroidsCYP24A1PPARDABCG1PPARGNR1H4ABCB11CYP2B6ABCB4CYP7A1CYP2B6CYP27B1ABCG5ABCA1CYP4A11ABCD3PPARAIsoprenoidsCYP8B1VDR7-DehydroCholesterolCYP7A1bta-mir-33abta-mir-33bbta-mir-33abta-mir-33b


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(78587) with a 92.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
107077view14:16, 17 September 2019MaintBotChEBI identifier normalization
105942view11:47, 16 August 2019MaintBotHMDB identifier normalization
96300view18:03, 7 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
80762view15:25, 30 June 2015Mkutmonhomology conversion
78597view14:51, 7 January 2015MaintBotadded missing graphIds
70173view00:42, 13 July 2013AlexanderPicoModified title
67542view11:23, 26 June 2013DdiglesOntology Term : 'lipid metabolic pathway' added !
63398view00:04, 10 May 2013MaintBotUpdated to 2013 gpml schema
48130view05:49, 9 May 2012MaintBotUpdating from human to fix xref duplication
40571view19:32, 1 March 2011MaintBotRemoved redundant pathway information and comments
35680view22:50, 12 February 2010KhanspersDescription
35678view22:49, 12 February 2010KhanspersModified description
33809view00:20, 9 December 2009MaintBotAutomatic update of empty xrefs
33625view10:03, 1 December 2009MaintBotRemoved group label
30550view21:59, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,25-Dihydroxy-Vitamins D3MetaboliteCHEBI:17823 (ChEBI)
7-DehydroCholesterolMetabolite434-16-2 (CAS)
ABCA1GeneProductENSBTAG00000020661 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:19
ABCB11GeneProductENSBTAG00000026885 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8647
ABCB1GeneProductENSBTAG00000005997 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5243
ABCB1aGeneProduct
ABCB4GeneProductENSBTAG00000005653 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5244
ABCC2GeneProduct
ABCC3GeneProduct
ABCD2GeneProductENSBTAG00000038043 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:225
ABCD3GeneProductENSBTAG00000009698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5825
ABCG1GeneProductENSBTAG00000021272 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9619
ABCG5GeneProductENSBTAG00000016365 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:64240
Acetyl CoAMetabolite72-89-9 (CAS)
Bile AcidsMetabolite3098 (ChEBI)
CYP1A2GeneProductENSBTAG00000000085 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1544
CYP24A1GeneProductENSBTAG00000002765 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1591
CYP26A1GeneProductENSBTAG00000021118 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1592
CYP27B1GeneProductENSBTAG00000016906 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1594
CYP2B6GeneProductENSBTAG00000003871 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1555
CYP2C9GeneProductENSBTAG00000020375 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1559
CYP2E1GeneProductENSBTAG00000018365 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1571
CYP3A4GeneProductENSBTAG00000047379 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1576
CYP4A11GeneProductENSBTAG00000000229 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1579
CYP4B1GeneProductENSBTAG00000011976 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1580
CYP7A1GeneProductENSBTAG00000005287 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1581
CYP8B1GeneProductENSBTAG00000034106 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1582
CholesterolMetabolite57-88-5 (CAS)
Fatty AcidsMetabolite35366 (ChEBI)
IsoprenoidsMetabolite24913 (ChEBI)
LanosterolMetabolite16521 (ChEBI)
NR1H3GeneProductENSBTAG00000010681 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10062
NR1H4GeneProductENSBTAG00000013596 (Ensembl)
  • Farnesoid X-activated receptor
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9971
NR1I2GeneProductENSBTAG00000019557 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8856
NR1I3GeneProductENSBTAG00000009215 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9970
OxysterolMetaboliteCHEBI:53030 (ChEBI)
PPARAGeneProductENSBTAG00000008063 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5465
PPARDGeneProductENSBTAG00000017542 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5467
PPARGGeneProductENSBTAG00000001333 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5468
RARAGeneProductENSBTAG00000012500 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5914
RARBGeneProductENSBTAG00000011518 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5915
RARGGeneProductENSBTAG00000007592 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5916
Retinoic acidMetaboliteHMDB01852 (HMDB)
SteroidsMetaboliteCHEBI:35341 (ChEBI)
VDRGeneProductENSBTAG00000016414 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7421
XenobioticsMetaboliteCHEBI:35703 (ChEBI)
abcg6GeneProduct
bta-mir-33aGeneProductENSBTAG00000029975 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000207932
bta-mir-33bGeneProductENSBTAG00000036437 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000207839

Annotated Interactions

No annotated interactions
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