Literature summary for 7.1.1.2 extracted from

Folbergrova, J.; Jesina, P.; Drahota, Z.; Lisy, V.; Haugvicova, R.; Vojtiskova, A.; Houstek, J.
Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures (2007), Exp. Neurol., 204, 597-609.

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Application

Application	Comment	Organism
medicine	inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury	Rattus norvegicus

Inhibitors

Inhibitors	Comment	Organism	Structure
DL-homocysteic acid	marked (ca. 64%) decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of DL-homocysteic acid (600 nanomol/side). Decrease is already evident during the acute phase of seizures (60-90 min after infusion) and persists for at least 20 h after the seizures. Inhibition is selective for complex I since activities of complex II and IV and citrate synthase remain unaffected. Inhibition of complex I activity is not associated with changes in complex I content. Enhanced production of reactive oxygen species by inhibited complex I in mitochondria from DL-homocysteic acid-treated animals. Competitive NMDA receptor antagonist AP7, a selective and potent group II mGluR agonist (2R,4R)-APDC and a highly selective group III mGluR, subtype 8, agonist (S)-3,4-DCPG, significantly reduce the extent of complex I inhibition. The superoxide dismutase mimetic Tempol and a selective peroxynitrite scavenger and decomposition catalyst FeTPPS provide a significant attenuation of complex I inhibition associated with DL-homocysteic acid-induced seizures	Rattus norvegicus
rotenone	rotenone-induced increment of H2O2 production is 2fold higher upon DL-homocysteic acid-treatment, thus clearly indicating elevated production of reactive oxygen species at complex I	Rattus norvegicus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Rattus norvegicus	5739	-

Organism

Organism	UniProt	Comment	Textmining
Rattus norvegicus	-	immature 12-day-old male Wistar albino rats	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
cerebral cortex	-	Rattus norvegicus	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
35.91	-	ca. 20 h survival after seizures	Rattus norvegicus
36.28	-	acute phase of seizures	Rattus norvegicus
100.6	-	controls	Rattus norvegicus
102	-	controls	Rattus norvegicus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
glutamate	-	Rattus norvegicus	?	-	?
malate	-	Rattus norvegicus	?	-	?
NADH + decyl-ubiquinone + H+	-	Rattus norvegicus	NAD+ + decyl-ubiquinol	-	?

Synonyms

Synonyms	Comment	Organism
complex I	-	Rattus norvegicus
NADH-ubiquinone oxidoreductase	-	Rattus norvegicus

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Release 2023.1 (January 2023)