Target metabolomics revealed complementary roles of hexose- and pentose-phosphates in the regulation of carbohydrate-dependent gene expression

American Journal of Physiology. Endocrinology and Metabolism
Santiago Diaz-MoralliMarta Cascante

Abstract

Carbohydrate response element-binding protein (ChREBP) is a transcription factor that mediates glucose signaling in mammalian liver, leading to the expression of different glycolytic and lipogenic genes, such as pyruvate kinase (L-PK) and fatty acid synthase (FAS). The current model for ChREBP activation in response to sugar phosphates holds that glucose metabolization to xylulose 5-phosphate (X-5-P) triggers the activation of protein phosphatase 2A, which dephosphorylates ChREBP and leads to its nuclear translocation and activation. However, evidence indicates that glucose 6-phosphate (G-6-P) is the most likely signal metabolite for the glucose-induced transcription of these genes. The glucose derivative that is responsible for carbohydrate-dependent gene expression remains to be identified. The difficulties in measuring G-6-P and X-5-P concentrations simultaneously and in changing them independently have hindered such identification. To discriminate between these possibilities, we adapted a liquid chromatography mass spectrometry method to identify and quantify sugar phosphates in human hepatocarcinoma cells (Hep G2) and rat hepatocytes in response to different carbon sources and in the presence/absence of a glucose-6-phospha...Continue Reading

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Citations

Sep 11, 2013·Trends in Cell Biology·Illana A StanleyNika N Danial
Jan 30, 2013·Pharmacology & Therapeutics·Santiago Diaz-MoralliMarta Cascante

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