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

• Published in: Metabolites Vol. 9; no. 12; p. 282
• Main Authors: Rajas, Fabienne, Gautier-Stein, Amandine, Mithieux, Gilles
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.11.2019; MDPI
• Subjects: Carbohydrate metabolism; carbohydrate response element-binding protein; Carbohydrates; chrebp; de novo lipogenesis; Diabetes; Diabetes mellitus (non-insulin dependent); Disease; Energy metabolism; Enzymes; Fasting; Fatty acids; Fatty liver; Glucose; Glucose metabolism; glucose production; Glycogen; glycogen storage disease type i; Glycolysis; Hepatocytes; hexosamine; Homeostasis; Hormones; Hyperglycemia; Hypoglycemia; Insulin; Kidneys; Kinases; Life Sciences; Lipid metabolism; Lipids; Lipogenesis; Liver; Liver diseases; Metabolic disorders; Metabolites; nafld; Neurons and Cognition; nonalcoholic fatty liver disease; Pentose phosphate pathway; Phosphorylation; Proteins; Review; steatosis; Storage diseases; Tumors; NAFLD; glycolysis; hexosamine; de novo lipogenesis; glycogen; pentose phosphate pathway; carbohydrate response element-binding protein; ChREBP; nonalcoholic fatty liver disease; glycogen storage disease type I; glucose production; diabetes; steatosis
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo9120282

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, 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.