The Tricarboxylic Acid Cycle, an Ancient Metabolic Network with a Novel Twist

Autor: Robert Hamel, Vasu D. Appanna, Ranji Singh, Daniel Chenier, Robin Beriault, Ryan J. Mailloux, Joseph Lemire
Rok vydání: 2007
Předmět:
Citric Acid Cycle
lcsh:Medicine
Dehydrogenase
Oxidative phosphorylation
Mitochondrion
Biology
Pseudomonas fluorescens
medicine.disease_cause
Cell Line
medicine
Homeostasis
Humans
Microbiology/Environmental Microbiology
lcsh:Science
Nuclear Magnetic Resonance
Biomolecular
Chromatography
High Pressure Liquid
chemistry.chemical_classification
Reactive oxygen species
Multidisciplinary
lcsh:R
Biochemistry/Chemical Biology of the Cell
Proteins
Vitamin K 3
Hydrogen Peroxide
Vitamins
Tricarboxylic acid
NAD
Oxidants
Citric acid cycle
Oxidative Stress
Isocitrate dehydrogenase
chemistry
Biochemistry
Metals
Ketoglutaric Acids
lcsh:Q
Microbiology/Microbial Physiology and Metabolism
Lipid Peroxidation
Reactive Oxygen Species
Oxidation-Reduction
Metabolic Networks and Pathways
Oxidative stress
Research Article
Zdroj: PLoS ONE
PLoS ONE, Vol 2, Iss 8, p e690 (2007)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0000690
Popis: 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.
Databáze: OpenAIRE
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