Preferred Label : Lipid Metabolism and Toxicity Pathway;
NCIt synonyms : Lipid Metabolism Pathway;
NCIt related terms : Nuclear Receptors in Lipid Metabolism and Toxicity;
Alternative definition : BIOCARTA: 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 receptors, which are responsible for lipid metabolism,
storage, and 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
requiring 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 catalyze 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 subsequent conversion to acetyl-p-benzoquinone imine (NAPQI) by
CYP1A2, CYP2E1 and CYP3A. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_nuclearRsPathway;
Origin ID : C39174;
UMLS CUI : C1517897;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
