Oxidative phosphorylation disorder

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Disorders of mitochondrial oxidative phosphorylation Proteins encoded by mitochondrial genes Proteins encoded by nuclear genes... 

Given the genetic and functional complexity and the fundamental role of mitochondria depicted above, it is not surprising that MRC disorders, or oxidative phosphorylation (OXPHOS) disorders, encompass a huge number of clinical presentations, possibly affecting any of the different body systems. 

Runaway mitochondria 1. Suppose that the mitochondria of a patient oxidizes NADH irrespective of whether ADP is present. The P 0 ratio for oxidative phosphorylation by these mitochondria is less than normal. Predict the likely symptoms of this disorder. 

A slowly progressive congenital neuromuscular disorder was reported in which the respiratory chain-linked energy transfer at a level common to all three energy coupling sites of respiratory chain was defective.52 Uncouplers of mitochondrial oxidative phosphorylation (2,4-dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone) (5) produced mitochondrial myopathy in rats.53... 

Pearson syndrome Systemic disorder of oxidative phosphorylation that predominantly affects bone marrow (same as above)... 

Ivy Sharer. In the case of Ivy Sharer, a diffuse myopathic process was ) superimposed on her AIDS and her pulmonary tuberculosis, either of which could have caused progressive weakness. In addition, she could have been suffering from a congenital mtDNA myopathy, symptomatic only as she ages. A systematic diagnostic process, however, finally led her physician to conclude that her myopathy was caused by a disorder of oxidative phosphorylation induced by her treatment with zidovndine (AZT). Fortunately, when AZT was discontinued, Ivy s myopathic symptoms gradually subsided. A repeat skeletal muscle biopsy performed 4 months later showed that her skeletal muscle cell mtDNA had been restored to normal and that she had experienced a reversible drug-induced disorder of oxidative phosphorylation. 

Beside the bactericidal function of nanosilver discussed in the literature, there are many factors that can cause the undesirable cytotoxicity effect of nanomaterials. The reason for silver s cytotoxicity should also be found in the formation of ROS, which damage the DNA and RNA of the cells by way of apoptosis. Due to the strong reduction-oxidation function (redox) of precious metals, nAg increase the ROS concentration and induce oxidation stress in the cells, initiating the peroxidation process, which causes a deformation of the cell membrane s structure, the latter s depolarization and the inhibition of the membrane enzymes activity. This leads to the loss in the integrity of the cell membrane and a disorder of the oxidative phosphorylation in mitochondria [6], which in consequence, contributes to cell degradation and leads to numerous diseases and accelerated ageing of the body [7]. 

Magnesium (Mg), the second intracellular cation after sodium, is a essential mineral. It is a critical cofactor in more than 300 enzymatic reactions. It may be required for substrate formation (Mg-ATP) and enzyme activation. It is critical for a great number of cellular functions, including oxidative phosphorylation, glycolysis, DNA transcription, and protein synthesis. It is involved in ion currents and membrane stabilization. Mg deficiency may be implicated in various metabolic disorders, including cardiovascular diseases, immune dysfunction and free radical damage. 

A muscle biopsy from a patient with the rare disorder, Luft disease, showed abnormally large mitochondria that contained packed cristae when examined in the electron microscope. Basal ATPase activity of the mitochodria was seven times greater than normal. From these and other data it was concluded that oxidation and phosphorylation were partially uncoupled. Which of the following statements about this patient is correct ... 

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