title: The consequences of a mild respiratory chain deficiency on substrate competitive oxidation in human mitochondria.
abstract: The competition between the respiratory substrates to gain access simultaneously to the respiratory chain depends on the dehydrogenase activity, the mitochondrial ubiquinone pool, and the oxidizing activity of the cytochrome segment. By studying the co-oxidation of NADH and succinate by control human liver homogenates, we found that a change in the balance between respiratory chain complex activities may affect significantly the ability of the mitochondria to oxidize one or the other substrate. Accordingly, in the particular case of a patient presenting with a partial complex I and IV deficiency, we observed a strongly reduced ability to oxidize NADH in the presence of succinate. It therefore appeared that even a slight imbalance between respiratory chain enzyme activities may result in a full blockade of a given substrate oxidation.
authors.affiliation: Unité de Recherches sur les Handicaps Génétique de l'Enfant, INSERM U393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Geromel
authors.forename: B
authors.initials: B
authors.lastname: Parfait
authors.forename: J C
authors.initials: JC
authors.lastname: von Kleist-Retzow
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
mesh_terms: D030401:Cytochrome-c Oxidase Deficiency; D005260:Female; D006801:Humans; D007223:Infant; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D013385:Succinate Dehydrogenase; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
chemical_list: D013386:Succinates; D009243:NAD; D019802:Succinic Acid; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone)