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Glucose-6 Phosphate, A Central Hub for Liver Carbohydrate Metabolism

1
Institut National de la Santé et de la Recherche Médicale, U1213, F-69008 Lyon, France
2
Université de Lyon, F-69008 Lyon, France
3
Université Lyon 1, F-69622 Villeurbanne, France
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(12), 282; https://doi.org/10.3390/metabo9120282
Received: 17 October 2019 / Revised: 14 November 2019 / Accepted: 18 November 2019 / Published: 20 November 2019
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
: Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease.
Keywords: de novo lipogenesis; carbohydrate response element-binding protein; ChREBP; diabetes; glucose production; glycogen; glycolysis; glycogen storage disease type I; hexosamine; nonalcoholic fatty liver disease; NAFLD; pentose phosphate pathway; steatosis de novo lipogenesis; carbohydrate response element-binding protein; ChREBP; diabetes; glucose production; glycogen; glycolysis; glycogen storage disease type I; hexosamine; nonalcoholic fatty liver disease; NAFLD; pentose phosphate pathway; steatosis
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MDPI and ACS Style

Rajas, F.; Gautier-Stein, A.; Mithieux, G. Glucose-6 Phosphate, A Central Hub for Liver Carbohydrate Metabolism. Metabolites 2019, 9, 282.

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