Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of copper over 2 h by normal lymphoid cells and those from Menkes'-disease patients (Menkes' cells) was found to be biphasic, with an initial phase of rapid uptake, an approach to steady state at around 40-60 min, followed by a further accumulation phase. The accumulation of copper was not diminished by the addition of a variety of metabolic inhibitors, suggesting that copper uptake is not an active process. The presence of carbonyl cyanide m-chlorophenylhydrazone in the culture medium stimulated the uptake and accumulation of copper in both normal and Menkes' cells to the same absolute level. This effect appeared to be specific for copper, since the accumulation of Zn and Cd was unaffected. Menkes' cells did not differ from normal in their initial rate of copper uptake. Analysis of the uptake curve suggested that the membrane transport of copper involves both passive and facilitated diffusion. Initial rate of efflux from the cells was approximated by two methods. Menkes' cells did not appear to be affected in this function. It seems likely that the basic defect in Menkes' disease involves a step in intracellular copper transport rather than the membrane transport of copper.
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PMID:Uptake and efflux of copper-64 in Menkes'-disease and normal continuous lymphoid cell lines. 342 41

The brindled mottled mouse (Mobr), an animal model of the Menkes' copper deficiency syndrome, was used for the investigation of changes in respiratory flux control associated with cytochrome c oxidase deficiency in muscle. Enzymatic analysis of cardiac and skeletal muscles showed an approximately 2-fold decrease in cytochrome c oxidase activity of brindled mutants in both types of muscles as compared with controls. The activities of NADH-cytochrome c oxidoreductase (respiratory chain segment I-III) and succinate-cytochrome c oxidoreductase (segment II-III) were normal. Assessment of mitochondrial respiratory function was performed using chemically skinned musculus quadriceps or heart muscle fibers isolated from control and brindled mottled mice. In skeletal muscle, there was no difference found in maximal rates of respiration. In the Mobr hearts, this parameter was slightly lower than control. Alternately, the determination of flux control coefficients of cytochrome c oxidase performed by a step by step inhibition of respiration with increasing concentrations of azide or cyanide revealed significantly sharper inhibition curves for brindled mice than for control, indicating more than 2-fold elevated flux control coefficients of cytochrome c oxidase. This investigation proved essential in characterizing the metabolic effect of a cytochrome c oxidase deficiency. We conclude, therefore, that application of metabolic control analysis can be a valuable approach to study defects of mitochondrial oxidative phosphorylation.
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PMID:Increase of flux control of cytochrome c oxidase in copper-deficient mottled brindled mice. 855 May 74