Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/HO in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria.

Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/HO in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria.

Publication date: Mar 07, 2019

According to recent findings, the human 2-oxoglutarate dehydrogenase complex (hOGDHc) could be an important source of the reactive oxygen species in the mitochondria and could contribute to mitochondrial abnormalities associated with multiple neurodegenerative diseases, including Alzheimer’s disease, Huntington disease, and Parkinson’s disease. The human 2-oxoadipate dehydrogenase (hE1a) is a novel protein, which is encoded by the DHTKD1 gene. Both missence and nonsense mutations were identified in the DHTKD1 that lead to alpha-aminoadipic and alpha-oxoadipic aciduria, a metabolic disorder with a wide variety of the neurological abnormalities, and Charcot-Marie-Tooth disease type 2Q, an inherited neurological disorder affecting the peripheral nervous system. Recently, the rare pathogenic mutations in DHTKD1 and an increased HO production were linked to the genetic ethiology of Eosinophilic Esophagitis (EoE), a chronic allergic inflammatory esophageal disorder. In view of the importance of hOGDHc in the tricarboxylic acid cycle (TCA cycle) and hE1a on the L-lysine, L-hydroxylysine and L-tryptophan degradation pathway in mitochondria, and to enhance our current understanding of the mechanism of superoxide/HO generation by hOGDHc, and by human 2-oxoadipate dehydrogenase complex (hOADHc), this review focuses on several novel and unanticipated recent findings in vitro that emerged from the Jordan group’s research. Most significantly, the hE1o and hE1a now join the hE3 as being able to generate the superoxide/HO in mitochondria.

Jordan, F., Nemeria, N., and Gerfen, G. Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/HO in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria. 06389. 2019 Neurochem Res.

Concepts Keywords
Allergic Alpha
Alzheimer Reactive oxygen species
Esophagitis Superoxide
Gene Mitochondrion
Genetic Oxoglutarate dehydrogenase complex
Huntington Lysine
Jordan DHTKD1
Lysine Cellular respiration
Metabolic Disorder Free radicals
Mitochondria Branches of biology
Mitochondrial Chemistry
Neurodegenerative Diseases Amino acids
Neurological Neurological disorder
Neurological Disorder Neurodegenerative diseases
Nonsense Mutations
Oxygen
Parkinson
Pathogenic
Peripheral Nervous System
Protein
Superoxide
TCA Cycle
Tricarboxylic Acid Cycle
Tryptophan

Semantics

Type Source Name
drug DRUGBANK Thiamine
drug DRUGBANK Hydrogen peroxide
disease DOID Huntington disease
disease MESH Huntington disease
disease MESH neurodegenerative diseases
pathway BSID Neurodegenerative Diseases
disease MESH multiple
disease MESH abnormalities
pathway BSID Oxidative Stress
disease MESH Oxidative Stress
drug DRUGBANK L-Lysine
pathway BSID TCA cycle
pathway BSID TCA Cycle
disease DOID Eosinophilic Esophagitis
disease MESH Eosinophilic Esophagitis
disease MESH neurological disorder
disease DOID Charcot-Marie-Tooth disease
disease MESH Charcot-Marie-Tooth disease
gene UNIPROT DHTKD1
disease MESH nonsense mutations

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *