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

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) f...

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Autores principales: Codocedo, Juan F., Landreth, Gary E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616595/
https://www.ncbi.nlm.nih.gov/pubmed/36337735
http://dx.doi.org/10.1097/IN9.0000000000000011
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author Codocedo, Juan F.
Landreth, Gary E.
author_facet Codocedo, Juan F.
Landreth, Gary E.
author_sort Codocedo, Juan F.
collection PubMed
description 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.
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spelling pubmed-96165952022-11-04 The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose Codocedo, Juan F. Landreth, Gary E. Immunometabolism (Cobham) Commentary 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. Lippincott Williams & Wilkins 2022-10-28 /pmc/articles/PMC9616595/ /pubmed/36337735 http://dx.doi.org/10.1097/IN9.0000000000000011 Text en Copyright © 2022 The Author(s), Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This paper is published under Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Commentary
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
title The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
title_full The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
title_fullStr The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
title_full_unstemmed The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
title_short The intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
title_sort intersection of metabolism and inflammation is governed by the intracellular topology of hexokinases and the metabolic fate of glucose
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616595/
https://www.ncbi.nlm.nih.gov/pubmed/36337735
http://dx.doi.org/10.1097/IN9.0000000000000011
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