Nuclear Receptors in Lipid Metabolism and Toxicity (Homo sapiens)

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DIETXenobioticsDIETGene expressionFatty AcidsCYP3A4Retinoic acidCholesterolSteroidsMIR33AABCG5CYP7A1VDRRARACYP4B1Acetyl CoAIsoprenoidsABCC3LanosterolBile AcidsCYP2C9ABCG1CYP2E1ABCA1NR1I2CYP2B6RARGABCA1CYP2C9CYP3A4CYP2B6ABCC2NR1H3RARBCYP7A1ABCB11CYP27B1CYP7A1CYP2C9MIR33BCYP3A4ABCD2abcg6PPARDCYP8B1ABCB1CYP24A1ABCB1aCYP4A11CYP1A27-DehydroCholesterolNR1H4ABCB4PPARAABCA1ABCD31,25-Dihydroxy-Vitamins D3NR1I3CYP26A1OxysterolPPARGMIR33AMIR33BMIR33AMIR33B


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.

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History

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CompareRevisionActionTimeUserComment
107139view14:22, 17 September 2019MaintBotChEBI identifier normalization
106730view13:21, 17 September 2019MaintBotHMDB identifier normalization
106665view21:26, 12 September 2019KhanspersModified description
105760view19:32, 15 August 2019KhanspersModified description
96301view18:20, 7 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
89331view09:59, 4 September 2016Mkutmonfix unconnected lines
78587view14:51, 7 January 2015MaintBotadded missing graphIds
78018view16:37, 11 November 2014EgonwAdded a few missing metabolite identifiers.
70027view01:54, 12 July 2013AlexanderPicoModified title
68978view17:42, 8 July 2013MaintBotUpdated to 2013 gpml schema
61677view21:32, 16 April 2013MaintBotremoved data source without identifer
59772view18:05, 7 March 2013EgonwConverted 'xenobiotics' to a DataNode and added the ChEBI id.
59771view17:56, 7 March 2013EgonwAdded two ChEBI ids for metabolite classes.
59184view18:51, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45336view20:19, 7 October 2011Khansperscleaned up description and removed old comment
45334view20:18, 7 October 2011KhanspersOntology Term : 'lipid metabolic pathway' added !
45143view01:11, 7 October 2011AlexanderPicoSpecify description
43564view23:09, 29 June 2011Samuel Sklarmir33 added
43563view22:54, 29 June 2011Samuel SklarPeriodical save, work in progress
41152view23:40, 1 March 2011MaintBotRemoved redundant pathway information and comments
38863view18:18, 24 September 2010KhanspersChanged line types
38862view18:16, 24 September 2010Khanspers
35672view22:46, 12 February 2010KhanspersDescription
35670view22:45, 12 February 2010KhanspersModified description
34436view18:16, 10 December 2009MaintBotAutomatic update of empty xrefs
32035view13:27, 14 August 2009MaintBotFixed group labels
21309view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:WP299]]: Moved to stable identifier
14008view17:20, 20 May 2008Thomasconnected lines
14006view17:13, 20 May 2008Thomasadded some metabolite annotations
13095view11:15, 17 May 2008MaintBotautomated metabolite conversion
8290view13:46, 7 January 2008MaintBot[[Pathway:Human:Nuclear receptors in lipid metabolism and toxicity]] moved to [[Pathway:Homo sapiens:Nuclear receptors in lipid metabolism and toxicity]]: Renaming species
7765view16:16, 18 December 2007MaintBotfixed category names
7381view12:42, 4 November 2007MaintBotAdded categories to GPML
6356view22:18, 22 May 2007S.Burelgpml file for [[Human:Nuclear_receptors_in_lipid_metabolism_and_toxicity]]

External references

DataNodes

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NameTypeDatabase referenceComment
1,25-Dihydroxy-Vitamins D3Metabolite
7-DehydroCholesterolMetabolite434-16-2 (CAS)
ABCA1GeneProduct19 (Entrez Gene)
ABCB11GeneProduct8647 (Entrez Gene)
ABCB1GeneProduct5243 (Entrez Gene)
ABCB1aGeneProduct
ABCB4GeneProduct5244 (Entrez Gene)
ABCC2GeneProduct1244 (Entrez Gene)
ABCC3GeneProduct8714 (Entrez Gene)
ABCD2GeneProduct225 (Entrez Gene)
ABCD3GeneProduct5825 (Entrez Gene)
ABCG1GeneProduct9619 (Entrez Gene)
ABCG5GeneProduct64240 (Entrez Gene)
Acetyl CoAMetabolite72-89-9 (CAS)
Bile AcidsMetabolite3098 (ChEBI)
CYP1A2GeneProduct1544 (Entrez Gene)
CYP24A1GeneProduct1591 (Entrez Gene)
CYP26A1GeneProduct1592 (Entrez Gene)
CYP27B1GeneProduct1594 (Entrez Gene)
CYP2B6GeneProduct1555 (Entrez Gene)
CYP2C9GeneProduct1559 (Entrez Gene)
CYP2E1GeneProduct1571 (Entrez Gene)
CYP3A4GeneProduct1576 (Entrez Gene)
CYP4A11GeneProduct1579 (Entrez Gene)
CYP4B1GeneProduct1580 (Entrez Gene)
CYP7A1GeneProduct1581 (Entrez Gene)
CYP8B1GeneProduct1582 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
Fatty AcidsMetabolite35366 (ChEBI)
IsoprenoidsMetabolite24913 (ChEBI)
LanosterolMetabolite6374 (ChEBI)
MIR33AGeneProductENSG00000207932 (Ensembl)
MIR33BGeneProductENSG00000207839 (Ensembl)
NR1H3GeneProduct10062 (Entrez Gene)
NR1H4GeneProduct9971 (Entrez Gene) Farnesoid X-activated receptor
NR1I2GeneProduct8856 (Entrez Gene)
NR1I3GeneProduct9970 (Entrez Gene)
OxysterolMetabolite
PPARAGeneProduct5465 (Entrez Gene)
PPARDGeneProduct5467 (Entrez Gene)
PPARGGeneProduct5468 (Entrez Gene)
RARAGeneProduct5914 (Entrez Gene)
RARBGeneProduct5915 (Entrez Gene)
RARGGeneProduct5916 (Entrez Gene)
Retinoic acidMetaboliteHMDB01852 (HMDB)
SteroidsMetabolite
VDRGeneProduct7421 (Entrez Gene)
abcg6GeneProduct

Annotated Interactions

No annotated interactions

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