The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose-Immunometabolism-CSCIED科技核心评价数据库-手机版

The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose

The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose

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DOI	10.1097/IN9.0000000000000011
刊名	Immunometabolism IJ
年，卷(期)	2022, 4(4)
作者	Codocedo, Juan F.; Landreth, Gary E.,
作者单位	[Codocedo, Juan F.; Landreth, Gary E.] Indiana Univ, Stark Neurosci Res Inst, Sch Med, Indianapolis, IN 46202 USA; [Codocedo, Juan F.; Landreth, Gary E.] Indiana Univ, Dept Anat Cell Biol & Physiol, Sch Med, Indianapolis, IN 46202 USA
摘要	Hexokinases (HKs) catalyze the first and irreversible step of glucose metabolism. Its product, glucose-6-phosphate (G-6P) serves as a precursor for catabolic processes like glycolysis for adenosine 5 '-triphosphate (ATP) production and anabolic pathways including the pentose phosphate pathway (PPP) for the generation of intermediaries like nicotinamide adenine dinucleotide phosphate (NADPH) and ribulose-5-P. Thus, the cellular fate of glucose is important not only for growth and maintenance, but also to determine different cellular activities. Studies in immune cells have demonstrated an intimate linkage between metabolic pathways and inflammation, however the precise molecular mechanisms that determine the cellular fate of glucose during inflammation or aging are not completely understood. Here we discuss a study by De Jesus et al that describes the role of HK1 cytosolic localization as a critical regulator of glucose flux by shunting glucose into the PPP at the expense of glycolysis, exacerbating the inflammatory response of macrophages. The authors convincingly demonstrate a novel mechanism that is independent of its mitochondrial functions, but involve the association to a protein complex that inhibits glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase. We expand the discussion by comparing previous studies related to the HK2 isoform and how cells have evolved to regulate the mitochondrial association of these two isoforms by non-redundant mechanism.
Abstract	Hexokinases (HKs) catalyze the first and irreversible step of glucose metabolism. Its product, glucose-6-phosphate (G-6P) serves as a precursor for catabolic processes like glycolysis for adenosine 5 '-triphosphate (ATP) production and anabolic pathways including the pentose phosphate pathway (PPP) for the generation of intermediaries like nicotinamide adenine dinucleotide phosphate (NADPH) and ribulose-5-P. Thus, the cellular fate of glucose is important not only for growth and maintenance, but also to determine different cellular activities. Studies in immune cells have demonstrated an intimate linkage between metabolic pathways and inflammation, however the precise molecular mechanisms that determine the cellular fate of glucose during inflammation or aging are not completely understood. Here we discuss a study by De Jesus et al that describes the role of HK1 cytosolic localization as a critical regulator of glucose flux by shunting glucose into the PPP at the expense of glycolysis, exacerbating the inflammatory response of macrophages. The authors convincingly demonstrate a novel mechanism that is independent of its mitochondrial functions, but involve the association to a protein complex that inhibits glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase. We expand the discussion by comparing previous studies related to the HK2 isoform and how cells have evolved to regulate the mitochondrial association of these two isoforms by non-redundant mechanism.
关键词	hexokinase; glucose
KeyWord	hexokinase; glucose
基金项目
页码	1-4

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引用本文

Codocedo, Juan F.; Landreth, Gary E.. The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose [J]. Immunometabolism. 2022; 4; (4). 1 - 4.

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