title: Aminoethylcysteine ketimine decarboxylated dimer inhibits mitochondrial respiration by impairing electron transport at complex I level.
abstract: The product of the spontaneous dimerization and decarboxylation of aminoethylcysteine ketimine (simply named the dimer in this note) has been investigated for a possible biochemical activity. It has been found that the dimer inhibits the ADP-dependent oxidation of NAD(+)-linked substrates in rat liver mitochondria and electron transport from NADH to O2 in bovine heart submitochondrial particles (SMP). Oxidation of succinate by SMP is not impaired by concentrations of the dimer inhibiting almost totally NADH oxidation. Furthermore, the dimer did not affect the rotenone-insensitive electron transfer from NADH to menadione. These results give a preliminary indication suggesting that the dimer inhibits electron flow from NADH dehydrogenase to ubiquinone at or near the rotenone binding site(s). The dimer inhibition falls in the same range exhibited by some neurotoxins which are known to interact with the rotenone binding site.
authors.affiliation: Dipartimento di Scienze Biochimiche, A. Rossi Fanelli, Università di Roma La Sapienza, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pecci
authors.forename: G
authors.initials: G
authors.lastname: Montefoschi
authors.forename: M
authors.initials: M
authors.lastname: Fontana
authors.forename: D
authors.initials: D
authors.lastname: Cavallini
mesh_terms: D000818:Animals; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism
chemical_list: C086349:5,9a-dihydro-5-oxopyrrolo(2,1-c-3,4-b')dithiomorpholine; D009025:Morpholines; D009097:Multienzyme Complexes; D013386:Succinates; D009243:NAD; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone)