title: Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice.
abstract: Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. Enzymatic analysis of cortex homogenates from Mo(vbr) mice showed an approximately twofold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities as compared with controls. Assessment of mitochondrial respiratory function was performed using digitonin-treated homogenates of the cortex, which exhibited the main characteristics of isolated brain mitochondria. Despite the substantial changes in respiratory chain enzyme activities, no significant differences were found in maximal pyruvate or succinate oxidation rates of brain cortex homogenates from Mo(vbr) and control mice. Inhibitor titrations were used to determine flux control coefficients of NADH:CoQ oxidoreductase and cytochrome c oxidase on the rate of mitochondrial respiration. Application of amobarbital to titrate the activity of NADH:CoQ oxidoreductase showed very similar flux control coefficients for control and mutant animals. Alternately, titration of respiration with azide revealed for Mo(vbr) mice significantly sharper inhibition curves than for controls, indicating a more than twofold elevated flux control coefficient of cytochrome c oxidase. Owing to the reserve capacity of respiratory chain enzymes, the reported changes in activities do not seem to affect whole-brain high-energy phosphates, as observed in a previous study using 31P NMR.
authors: Department of Epileptology, University of Bonn Medical Center, Germany.
authors: W S
authors: WS
authors: Kunz
authors: A V
authors: AV
authors: Kuznetsov
authors: J F
authors: JF
authors: Clark
authors: I
authors: I
authors: Tracey
authors: C E
authors: CE
authors: Elger
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D003300:Copper / Q000172:deficiency*; D030401:Cytochrome-c Oxidase Deficiency; D003600:Cytosol / Q000201:enzymology; D042967:Electron Transport Complex I; D004789:Enzyme Activation / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D010759:Phosphorus Isotopes; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D010759:Phosphorus Isotopes; D003300:Copper; D019802:Succinic Acid; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I