author_facet Sonnewald, Ursula
Sonnewald, Ursula
author Sonnewald, Ursula
spellingShingle Sonnewald, Ursula
Journal of Neurochemistry
Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
Cellular and Molecular Neuroscience
Biochemistry
author_sort sonnewald, ursula
spelling Sonnewald, Ursula 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/jnc.12812 <jats:title>Abstract</jats:title><jats:p>The central process in energy production is the oxidation of acetyl‐CoA to <jats:styled-content style="fixed-case">CO</jats:styled-content><jats:sub>2</jats:sub> by the tricarboxylic acid (<jats:styled-content style="fixed-case">TCA</jats:styled-content>, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, <jats:styled-content style="fixed-case">GABA</jats:styled-content>, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in the brain. When <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle ketoacids are removed, they must be replaced to permit the continued function of this essential pathway, by a process termed <jats:italic>anaplerosis</jats:italic>. Since the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle cannot act as a carbon sink, <jats:italic>anaplerosis</jats:italic> must be coupled with <jats:italic>cataplerosis</jats:italic>; the exit of intermediates from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle. The role of anaplerotic reactions for cellular metabolism in the brain has been studied extensively. However, the coupling of this process with <jats:italic>cataplerosis</jats:italic> and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between <jats:italic>anaplerosis</jats:italic> and <jats:italic>cataplerosis</jats:italic> should be underscored, because the balance between these two processes is essential. The hypothesis that <jats:italic>cataplerosis</jats:italic> in the brain is achieved by exporting the lactate generated from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle intermediates into the blood and perivascular area is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12812-fig-0005-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Intermediates leave the tricarboxylic acid cycle and must be replaced by a process termed <jats:italic>anaplerosis</jats:italic> that must be coupled to cataplerosis. We hypothesize that <jats:italic>cataplerosis</jats:italic> is achieved by exporting the lactate generated from the cycle into the blood and perivascular area. This shifts the paradigm of lactate generation as solely derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.</jats:p> Glutamate synthesis has to be matched by its degradation – where do all the carbons go? Journal of Neurochemistry
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title Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_unstemmed Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_full Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_fullStr Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_full_unstemmed Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_short Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_sort glutamate synthesis has to be matched by its degradation – where do all the carbons go?
topic Cellular and Molecular Neuroscience
Biochemistry
url http://dx.doi.org/10.1111/jnc.12812
publishDate 2014
physical 399-406
description <jats:title>Abstract</jats:title><jats:p>The central process in energy production is the oxidation of acetyl‐CoA to <jats:styled-content style="fixed-case">CO</jats:styled-content><jats:sub>2</jats:sub> by the tricarboxylic acid (<jats:styled-content style="fixed-case">TCA</jats:styled-content>, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, <jats:styled-content style="fixed-case">GABA</jats:styled-content>, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in the brain. When <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle ketoacids are removed, they must be replaced to permit the continued function of this essential pathway, by a process termed <jats:italic>anaplerosis</jats:italic>. Since the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle cannot act as a carbon sink, <jats:italic>anaplerosis</jats:italic> must be coupled with <jats:italic>cataplerosis</jats:italic>; the exit of intermediates from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle. The role of anaplerotic reactions for cellular metabolism in the brain has been studied extensively. However, the coupling of this process with <jats:italic>cataplerosis</jats:italic> and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between <jats:italic>anaplerosis</jats:italic> and <jats:italic>cataplerosis</jats:italic> should be underscored, because the balance between these two processes is essential. The hypothesis that <jats:italic>cataplerosis</jats:italic> in the brain is achieved by exporting the lactate generated from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle intermediates into the blood and perivascular area is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12812-fig-0005-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Intermediates leave the tricarboxylic acid cycle and must be replaced by a process termed <jats:italic>anaplerosis</jats:italic> that must be coupled to cataplerosis. We hypothesize that <jats:italic>cataplerosis</jats:italic> is achieved by exporting the lactate generated from the cycle into the blood and perivascular area. This shifts the paradigm of lactate generation as solely derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.</jats:p>
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author Sonnewald, Ursula
author_facet Sonnewald, Ursula, Sonnewald, Ursula
author_sort sonnewald, ursula
container_issue 4
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container_title Journal of Neurochemistry
container_volume 131
description <jats:title>Abstract</jats:title><jats:p>The central process in energy production is the oxidation of acetyl‐CoA to <jats:styled-content style="fixed-case">CO</jats:styled-content><jats:sub>2</jats:sub> by the tricarboxylic acid (<jats:styled-content style="fixed-case">TCA</jats:styled-content>, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, <jats:styled-content style="fixed-case">GABA</jats:styled-content>, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in the brain. When <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle ketoacids are removed, they must be replaced to permit the continued function of this essential pathway, by a process termed <jats:italic>anaplerosis</jats:italic>. Since the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle cannot act as a carbon sink, <jats:italic>anaplerosis</jats:italic> must be coupled with <jats:italic>cataplerosis</jats:italic>; the exit of intermediates from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle. The role of anaplerotic reactions for cellular metabolism in the brain has been studied extensively. However, the coupling of this process with <jats:italic>cataplerosis</jats:italic> and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between <jats:italic>anaplerosis</jats:italic> and <jats:italic>cataplerosis</jats:italic> should be underscored, because the balance between these two processes is essential. The hypothesis that <jats:italic>cataplerosis</jats:italic> in the brain is achieved by exporting the lactate generated from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle intermediates into the blood and perivascular area is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12812-fig-0005-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Intermediates leave the tricarboxylic acid cycle and must be replaced by a process termed <jats:italic>anaplerosis</jats:italic> that must be coupled to cataplerosis. We hypothesize that <jats:italic>cataplerosis</jats:italic> is achieved by exporting the lactate generated from the cycle into the blood and perivascular area. This shifts the paradigm of lactate generation as solely derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.</jats:p>
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spelling Sonnewald, Ursula 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/jnc.12812 <jats:title>Abstract</jats:title><jats:p>The central process in energy production is the oxidation of acetyl‐CoA to <jats:styled-content style="fixed-case">CO</jats:styled-content><jats:sub>2</jats:sub> by the tricarboxylic acid (<jats:styled-content style="fixed-case">TCA</jats:styled-content>, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, <jats:styled-content style="fixed-case">GABA</jats:styled-content>, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in the brain. When <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle ketoacids are removed, they must be replaced to permit the continued function of this essential pathway, by a process termed <jats:italic>anaplerosis</jats:italic>. Since the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle cannot act as a carbon sink, <jats:italic>anaplerosis</jats:italic> must be coupled with <jats:italic>cataplerosis</jats:italic>; the exit of intermediates from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle. The role of anaplerotic reactions for cellular metabolism in the brain has been studied extensively. However, the coupling of this process with <jats:italic>cataplerosis</jats:italic> and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between <jats:italic>anaplerosis</jats:italic> and <jats:italic>cataplerosis</jats:italic> should be underscored, because the balance between these two processes is essential. The hypothesis that <jats:italic>cataplerosis</jats:italic> in the brain is achieved by exporting the lactate generated from the <jats:styled-content style="fixed-case">TCA</jats:styled-content> cycle intermediates into the blood and perivascular area is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12812-fig-0005-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Intermediates leave the tricarboxylic acid cycle and must be replaced by a process termed <jats:italic>anaplerosis</jats:italic> that must be coupled to cataplerosis. We hypothesize that <jats:italic>cataplerosis</jats:italic> is achieved by exporting the lactate generated from the cycle into the blood and perivascular area. This shifts the paradigm of lactate generation as solely derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.</jats:p> Glutamate synthesis has to be matched by its degradation – where do all the carbons go? Journal of Neurochemistry
spellingShingle Sonnewald, Ursula, Journal of Neurochemistry, Glutamate synthesis has to be matched by its degradation – where do all the carbons go?, Cellular and Molecular Neuroscience, Biochemistry
title Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_full Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_fullStr Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_full_unstemmed Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_short Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_sort glutamate synthesis has to be matched by its degradation – where do all the carbons go?
title_unstemmed Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
topic Cellular and Molecular Neuroscience, Biochemistry
url http://dx.doi.org/10.1111/jnc.12812