Cited by 434Biochemical Acid Research StudiesMitochondrial Function and PathologyRedox biology and oxidative stress

Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress

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Tretter, Laszlo, Adam-Vizi, Vera·2005·Philosophical Transactions of the Royal Society B: Biological Sciences

Abstract

Alpha-ketoglutarate dehydrogenase (α-KGDH) is a highly regulated enzyme, which could determine the metabolic flux through the Krebs cycle. It catalyses the conversion of α-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain. α-KGDH is sensitive to reactive oxygen species (ROS) and inhibition of this enzyme could be critical in the metabolic deficiency induced by oxidative stress. Aconitase in the Krebs cycle is more vulnerable than α-KGDH to ROS but as long as α-KGDH is functional NADH generation in the Krebs cycle is maintained. NADH supply to the respiratory chain is limited only when α-KGDH is also inhibited by ROS. In addition being a key target, α-KGDH is able to generate ROS during its catalytic function, which is regulated by the NADH/NAD + ratio. The pathological relevance of these two features of α-KGDH is discussed in this review, particularly in relation to neurodegeneration, as an impaired function of this enzyme has been found to be characteristic for several neurodegenerative diseases.

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Crossref · 10.1098/rstb.2005.1764

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  • Other mitochondrial proteins, including the TCA cycle enzymes α-KGDH and aconitase, are especially sensitive to oxidative inactivation.

    “Other mitochondrial proteins, including the TCA cycle enzymes α-KGDH and aconitase, are especially sensitive to oxidative inactivation (423).”

    From Redox regulation of mitochondrial function (2012) · cites this paper as [423]

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Authors
Tretter, L., & Adam-Vizi, V.
Affiliations
Department of Medical Biochemistry, Szentagothai Janos Knowledge Center, Semmelweis University and Neurobiochemical Group, Hungarian Academy of SciencesPO Box 262, Budapest 1444, Hungary
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Published
2005-11-04
Volume
360
Issue
1464
Pages
2335-2345
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
OpenAlex
W2156107840
Cited by
434
References
128
Citations by year
2026: 21 · 2025: 31 · 2024: 25 · 2023: 29 · 2022: 31 · 2021: 41 · 2020: 27 · 2019: 26 · 2018: 18 · 2017: 34 · 2016: 20 · 2015: 17 · 2014: 24 · 2013: 10 · 2012: 10
FWCI
4.25
Type
journal article
Language
en
Open access
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Hungarian Scientific Research Fund
  • Magyar Tudományos Akadémia
  • Nemzeti Kutatási és Technológiai Hivatal
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
alpha-ketoglutarate dehydrogenase, oxidative stress, reactive oxygen species, TCA cycle, NADH generation, electron transport chain, aconitase, NAD+/NADH ratio, enzyme inhibition, neurodegenerative diseases, metabolic regulation
MeSH terms
Citric Acid Cycle, Humans, Ketoglutarate Dehydrogenase Complex, Mitochondria, NAD, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases

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