Preferred Label : ChREBP Pathway;
NCIt related terms : ChREBP regulation by carbohydrates and cAMP;
Alternative definition : BIOCARTA: Although insulin and glucagon play important roles in regulating the response
of cells to nutrients, cells also respond to carbohydrates through transcriptional
regulation by the glucose responsive transcription factor ChREBP. ChREBP, carbohydrate
responsive element binding protein, is a transcription factor that is activated by
high levels of carbohydrates and repressed by cAMP. The activation of ChREBP by elevated
carbohydrate levels increases the activity of genes involved in glucose metabolism
such as pyruvate kinase, a rate-limiting enzyme in glycolysis, increasing the overall
rate of utilization of carbohydrates. Excess carbohydrates also increase the transcription
of genes that convert carbohydrates to triglycerides in the liver for storage in adipose
tissue. cAMP regulates ChREBP activity by activating PKA, which phosphorylates ChREBP.
Phosphorylation of ChREBP at ser(196) inactivates nuclear import and phosphorylation
at Thr(666) prevents DNA binding by ChREBP. A metabolite of glucose activates protein
phosphatase PP2A that then dephosphorylates both sites on ChREBP in response to increased
glucose levels and increases ChREBP activity. Other pathways also regulate ChREBP
activity and response to nutrients. High fat diets repress ChREBP activation by increasing
AMP in liver cells, activating the AMP kinase. Phosphorylation of ChREBP by AMP kinase
inactivates ChREBP and blocks glucose induction of ChREBP, linking dietary fatty acids
to the regulation of carbohydrate metabolism. (This definition may be outdated - see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Definition might be outdated or inaccurate.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_chrebpPathway;
Origin ID : C39029;
UMLS CUI : C1516440;
Semantic type(s)
has_gene_product_element
pathway_has_gene_element