The mitochondrial energy-generating system (MEGS) encompasses the mitochondrial enzymatic reactions from oxidation of pyruvate to the export of adenosine triphosphate. It is investigated in intact muscle mitochondria by measuring the pyruvate oxidation and adenosine triphosphate production rates, which we refer to as the "MEGS capacity." Currently, little is known about MEGS pathology in patients with mutations in the mitochondrial DNA. Because MEGS capacity is an indicator for the overall mitochondrial function related to energy production, we searched for a correlation between MEGS capacity and 3243A-->G mutation load in muscle of patients with the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome.
In muscle tissue of 24 patients with the 3243A-->G mutation, we investigated the MEGS capacity, the respiratory chain enzymatic activities, and the 3243A-->G mutation load. To exclude coinciding mutations, we sequenced all 22 mitochondrial transfer RNA genes in the patients, if possible.
We found highly significant differences between patients and control subjects with respect to the MEGS capacity and complex I, III, and IV activities. MEGS-related measurements correlated considerably better with the mutation load than respiratory chain enzyme activities. We found no additional mutations in the mitochondrial transfer RNA genes of the patients.
The results show that MEGS capacity has a greater sensitivity than respiratory chain enzymatic activities for detection of subtle mitochondrial dysfunction. This is important in the workup of patients with rare or new mitochondrial DNA mutations, and with low mutation loads. In these cases we suggest to determine the MEGS capacity.
"A reduced pyruvate oxidation rate that is normalized by addition of an uncoupler, such as FCCP, indicates a defect in complex V, the adenine nucleotide translocator, or the phosphate transporter (Jonckheere et al. 2008; Mayr et al. 2007). The MEGS assays described above not only provide in-depth information on the mitochondrial functional state, it has also been shown that these assays are more sensitive to detect mitochondrial defects, compared to measurements of individual OXPHOS enzyme activities (Janssen et al. 2008). In the case of a patient with a clinical phenotype with profound involvement of tissues other than muscle, a biopsy of the affected tissue should be considered. "
[Show abstract][Hide abstract] ABSTRACT: Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patients requires a multi-disciplinary clinical and laboratory evaluation in which the biochemical examination of the mitochondrial functional state often plays a central role. In most cases, a muscle biopsy provides the best opportunity to examine mitochondrial function. In addition to activity measurements of individual oxidative phosphorylation enzymes, analysis of mitochondrial respiration, substrate oxidation, and ATP production rates is performed to obtain a detailed picture of the mitochondrial energy-generating system. On the basis of the compilation of clinical, biochemical, and other laboratory test results, candidate genes are selected for molecular genetic testing. In patients in whom an unknown genetic variant is identified, a compatible biochemical phenotype is often required to firmly establish the diagnosis. In addition to the current role of the biochemical analysis in the diagnostic examination of patients with a suspected mitochondria disorder, this report gives a future perspective on the biochemical diagnosis in view of both the expanding genotypes of mitochondrial disorders and the possibilities for high throughput molecular genetic diagnosis.
[Show abstract][Hide abstract] ABSTRACT: The physisorption and chemisorption of hydrogen on two types of Y-junction carbon nanotubes(Y-(6,6) and Y(10,0)) have been studied using molecular dynamics (MD) simulations and semiempirical (AM1) method. The MD simulations study show that H<sub>2</sub> molecule can penetrate into the open ends of the branches and stay inside even at room temperature, which is confirmed by the study of potential energies for different pathways with AM1 method. Furthermore, the potential energy variation of H<sub>2</sub> penetrating into the open end along the axis of one branch arm is quite similar to that of H<sub>2</sub> in straight carbon nanotubes. The study of chemisorption of hydrogen atoms on Y (6,6) indicates that the carbon atoms in the heptagons are more active to bind hydrogen atoms. It has been also found that the neighboring carbon atoms of Y (6,6) prefer to bind two hydrogen atoms.
Nanotechnology, 2003. IEEE-NANO 2003. 2003 Third IEEE Conference on; 09/2003
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