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Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species
Joint Authors
Berndt, Nikolaus
Bulik, Sascha
Holzhütter, Hermann-Georg
Source
International Journal of Cell Biology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-10
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease.
In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model.
Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential.
By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters.
As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production.
The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition.
Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases.
American Psychological Association (APA)
Berndt, Nikolaus& Bulik, Sascha& Holzhütter, Hermann-Georg. 2012. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-496363
Modern Language Association (MLA)
Berndt, Nikolaus…[et al.]. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-496363
American Medical Association (AMA)
Berndt, Nikolaus& Bulik, Sascha& Holzhütter, Hermann-Georg. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-496363
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-496363