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Literature summary for 1.2.1.105 extracted from

  • Jeitner, T.M.; Xu, H.; Gibson, G.E.
    Inhibition of the alpha-ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono-N-chloramine (2005), J. Neurochem., 92, 302-310.
    View publication on PubMed

Application

Application Comment Organism
medicine hypochlorous acid and chloramines have the potential to inactivate KGDHC, a major target in neurodegeneration Sus scrofa
medicine hypochlorous acid and chloramines have the potential to inactivate KGDHC, a major target in neurodegeneration, without significant loss of cellular viability Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
H2O2 inhibits lysate KGDHC in a concentration- and time-dependent manner, inhibitory effect reversed by addition of dithiothreitol Mus musculus
H2O2 ca. 300 times less effective than mono-N-chloramine Sus scrofa
hypochlorous acid myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vivo Homo sapiens
hypochlorous acid concentration-dependent monophasic inhibition Mus musculus
hypochlorous acid inhibits at concentrations ca. 50 times less than the effective mono-N-chloramine concentrations; myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vitro Sus scrofa
mono-N-chloramine myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vivo Homo sapiens
mono-N-chloramine inhibits both lysate and in situ KGDHC activities in a concentration-dependent manner in three distinct phases Mus musculus
mono-N-chloramine inhibits in a time- and concentration-dependent manner; myeloperoxidase product, inhibition of the alpha-ketoglutarate dehydrogenase multienzyme complex in vitro Sus scrofa

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+
-
Homo sapiens
Mg2+
-
Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine Homo sapiens
-
[dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
-
ir
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine Sus scrofa
-
[dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
-
ir
additional information Homo sapiens loss of enzyme activity contributes to the major loss of cerebral energy metabolism leading to a number of neurodegenerative disorders and Alzheimer's disease, myeloperoxidase activity is involved ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-
Sus scrofa
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
additional information resulting in loss of enzyme complex activity Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
-
Sus scrofa

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-
heart
-
Sus scrofa
-
microglia
-
Homo sapiens
-
additional information N2a cells Mus musculus
-
Neuro-2a cell neuroblastoma cells Mus musculus
-
neuron
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine
-
Homo sapiens [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
-
ir
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine
-
Sus scrofa [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
-
ir
additional information loss of enzyme activity contributes to the major loss of cerebral energy metabolism leading to a number of neurodegenerative disorders and Alzheimer's disease, myeloperoxidase activity is involved Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
alpha-ketoglutarate dehydrogenase complex
-
Mus musculus
alpha-ketoglutarate dehydrogenase complex
-
Homo sapiens
alpha-ketoglutarate dehydrogenase complex
-
Sus scrofa
KGDHC
-
Mus musculus
KGDHC
-
Homo sapiens
KGDHC
-
Sus scrofa

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Sus scrofa
37
-
in vivo assay at, N2a cells Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Sus scrofa
7.4
-
in vivo assay at, N2a cells Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Homo sapiens
NAD+
-
Sus scrofa
thiamine diphosphate
-
Sus scrofa
thiamine diphosphate thiamine deficiency results in decreased enzyme complex activity and selective neuronal loss Homo sapiens