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Cerebral Gluconeogenesis and Diseases

The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also d...

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Autores principales: Yip, James, Geng, Xiaokun, Shen, Jiamei, Ding, Yuchuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209353/
https://www.ncbi.nlm.nih.gov/pubmed/28101056
http://dx.doi.org/10.3389/fphar.2016.00521
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author Yip, James
Geng, Xiaokun
Shen, Jiamei
Ding, Yuchuan
author_facet Yip, James
Geng, Xiaokun
Shen, Jiamei
Ding, Yuchuan
author_sort Yip, James
collection PubMed
description The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions.
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spelling pubmed-52093532017-01-18 Cerebral Gluconeogenesis and Diseases Yip, James Geng, Xiaokun Shen, Jiamei Ding, Yuchuan Front Pharmacol Pharmacology The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions. Frontiers Media S.A. 2017-01-04 /pmc/articles/PMC5209353/ /pubmed/28101056 http://dx.doi.org/10.3389/fphar.2016.00521 Text en Copyright © 2017 Yip, Geng, Shen and Ding. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yip, James
Geng, Xiaokun
Shen, Jiamei
Ding, Yuchuan
Cerebral Gluconeogenesis and Diseases
title Cerebral Gluconeogenesis and Diseases
title_full Cerebral Gluconeogenesis and Diseases
title_fullStr Cerebral Gluconeogenesis and Diseases
title_full_unstemmed Cerebral Gluconeogenesis and Diseases
title_short Cerebral Gluconeogenesis and Diseases
title_sort cerebral gluconeogenesis and diseases
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209353/
https://www.ncbi.nlm.nih.gov/pubmed/28101056
http://dx.doi.org/10.3389/fphar.2016.00521
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