A31P-magnetic resonance spectroscopy and biochemical study of the movbr mouse: Potential model for the mitochondrial encephalomyopathies

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 31 P NMR. Key Words: Cytochrome c oxidase deficiency-Brain mitochondria-Oxidative phosphorylation-Copper deficiency-Flux control coefficients.

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A31P-magnetic resonance spectroscopy and biochemical study of the movbr mouse: Potential model for the mitochondrial encephalomyopathies

Cited by 8 publications

References 28 publications

Development of NMR: Biological and Medical MR Spectroscopy

Development of NMR: Biological and Medical MR Spectroscopy

Generation of Transmitochondrial Mice: Development of Xenomitochondrial Mice to Model Neurodegenerative Diseases

Metabolic Consequences of the CytochromecOxidase Deficiency in Brain of Copper‐Deficient Mo^vbrMice

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A31P-magnetic resonance spectroscopy and biochemical study of the movbr mouse: Potential model for the mitochondrial encephalomyopathies

Cited by 8 publications

References 28 publications

Development of NMR: Biological and Medical MR Spectroscopy

Development of NMR: Biological and Medical MR Spectroscopy

Generation of Transmitochondrial Mice: Development of Xenomitochondrial Mice to Model Neurodegenerative Diseases

Metabolic Consequences of the CytochromecOxidase Deficiency in Brain of Copper‐Deficient MovbrMice

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Product

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About

Metabolic Consequences of the CytochromecOxidase Deficiency in Brain of Copper‐Deficient Mo^vbrMice