The tricarboxylic acid cycle, an ancient metabolic network with a novel twist.
The tricarboxylic acid (TCA) cycle is an essential metabolic network in all oxidative organisms and provides precursors for anabolic processes and reducing factors (NADH and FADH(2)) that drive the generation of energy. Here, we show that this metabolic network is also an integral part of the oxidat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-08-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC1930152?pdf=render |
| _version_ | 1818935680362872832 |
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| author | Ryan J Mailloux Robin Bériault Joseph Lemire Ranji Singh Daniel R Chénier Robert D Hamel Vasu D Appanna |
| author_facet | Ryan J Mailloux Robin Bériault Joseph Lemire Ranji Singh Daniel R Chénier Robert D Hamel Vasu D Appanna |
| author_sort | Ryan J Mailloux |
| collection | DOAJ |
| description | The tricarboxylic acid (TCA) cycle is an essential metabolic network in all oxidative organisms and provides precursors for anabolic processes and reducing factors (NADH and FADH(2)) that drive the generation of energy. Here, we show that this metabolic network is also an integral part of the oxidative defence machinery in living organisms and alpha-ketoglutarate (KG) is a key participant in the detoxification of reactive oxygen species (ROS). Its utilization as an anti-oxidant can effectively diminish ROS and curtail the formation of NADH, a situation that further impedes the release of ROS via oxidative phosphorylation. Thus, the increased production of KG mediated by NADP-dependent isocitrate dehydrogenase (NADP-ICDH) and its decreased utilization via the TCA cycle confer a unique strategy to modulate the cellular redox environment. Activities of alpha-ketoglutarate dehydrogenase (KGDH), NAD-dependent isocitrate dehydrogenase (NAD-ICDH), and succinate dehydrogenase (SDH) were sharply diminished in the cellular systems exposed to conditions conducive to oxidative stress. These findings uncover an intricate link between TCA cycle and ROS homeostasis and may help explain the ineffective TCA cycle that characterizes various pathological conditions and ageing. |
| first_indexed | 2024-12-20T05:24:01Z |
| format | Article |
| id | doaj.art-862f5883fbae4185ab36ac2a4b7eafdb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T05:24:01Z |
| publishDate | 2007-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-862f5883fbae4185ab36ac2a4b7eafdb2022-12-21T19:51:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-08-0128e69010.1371/journal.pone.0000690The tricarboxylic acid cycle, an ancient metabolic network with a novel twist.Ryan J MaillouxRobin BériaultJoseph LemireRanji SinghDaniel R ChénierRobert D HamelVasu D AppannaThe tricarboxylic acid (TCA) cycle is an essential metabolic network in all oxidative organisms and provides precursors for anabolic processes and reducing factors (NADH and FADH(2)) that drive the generation of energy. Here, we show that this metabolic network is also an integral part of the oxidative defence machinery in living organisms and alpha-ketoglutarate (KG) is a key participant in the detoxification of reactive oxygen species (ROS). Its utilization as an anti-oxidant can effectively diminish ROS and curtail the formation of NADH, a situation that further impedes the release of ROS via oxidative phosphorylation. Thus, the increased production of KG mediated by NADP-dependent isocitrate dehydrogenase (NADP-ICDH) and its decreased utilization via the TCA cycle confer a unique strategy to modulate the cellular redox environment. Activities of alpha-ketoglutarate dehydrogenase (KGDH), NAD-dependent isocitrate dehydrogenase (NAD-ICDH), and succinate dehydrogenase (SDH) were sharply diminished in the cellular systems exposed to conditions conducive to oxidative stress. These findings uncover an intricate link between TCA cycle and ROS homeostasis and may help explain the ineffective TCA cycle that characterizes various pathological conditions and ageing.http://europepmc.org/articles/PMC1930152?pdf=render |
| spellingShingle | Ryan J Mailloux Robin Bériault Joseph Lemire Ranji Singh Daniel R Chénier Robert D Hamel Vasu D Appanna The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. PLoS ONE |
| title | The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. |
| title_full | The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. |
| title_fullStr | The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. |
| title_full_unstemmed | The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. |
| title_short | The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. |
| title_sort | tricarboxylic acid cycle an ancient metabolic network with a novel twist |
| url | http://europepmc.org/articles/PMC1930152?pdf=render |
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