Mitochondria diseases

Phosphorus-31 MRS has been used widely to investigate mitochondria diseases in muscle. Trenell et al. measured an elevated ADP concentration and pHi in a group of mitochondrial myopathy (MM) patients, which is evidence of impaired oxidative ATP production in their skeletal mus-cle This study also showed that increased inspired oxygen concentration improves oxidative fimction in MM patients. In a separate study, Jeppesen et al. could not differentiate healthy subjects and MM patients using P MRS. ° They concluded the P MRS should not be a routine test in the diagnosis for MM patients. 

Mitochondrial DNA is inherited maternally. What makes mitochondrial diseases particularly interesting from a genetic point of view is that the mitochondrion has its own DNA (mtDNA) and its own transcription and translation processes. The mtDNA encodes only 13 polypeptides nuclear DNA (nDNA) controls the synthesis of 90-95% of all mitochondrial proteins. All known mito-chondrially encoded polypeptides are located in the inner mitochondrial membrane as subunits of the respiratory chain complexes (Fig. 42-3), including seven subunits of complex I the apoprotein of cytochrome b the three larger subunits of cytochrome c oxidase, also termed complex IV and two subunits of ATPase, also termed complex V. 

It seems worthwhile to explore these ideas further. It would need the investigation of the pathway and rds for the reduction of 02 on some artificial membranes that simulate suspected reaction centers in the mitochondrion. A pan-electrochemical explanation of degenerative diseases would be to see them in terms of a slowdown of the bioelectrocatalysts of the 02 reduction. To that extent that age and accumulated fragments reduce the velocity of the enzymatic reduction of 02, is it likely that an excess 02 remains left over to form peroxy radicals and damage cells. 

Aliev G, Smith MA, de la Torre JC, Perry G (2004) Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer s disease. Mitochondrion 4 649-663 Allen DD, Galdzicki Z, Brining SK, Fukuyama R, Rapoport SI, Smith QR (1997) Beta-amyloid induced increase in choline flux across PCD cell membranes. Neurosd Lett 234 71-73 Alonso AC, Grundke-Iqbal I, Iqbal K (1996) Alzheimer s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 2 783-787... 

Protoporphyrinogen oxidase converts protoporphyrinogen IX to the fully desaturated porphyrin in a reaction that uses O2 as the terminal electron acceptor (Fig. 3). The crystal structure of the homodimeric enzyme shows it has one FAD per monomer, which presumably mediates the porphyrin oxidation reaction (19). Like the decarboxylation mediated by coproporphyrinogen oxidase, this reaction also occurs in the mitochondrion. Mutations in the protoporphyrinogen oxidase gene are responsible for variegate porphyria (21). Acute attacks of this disease can be effectively treated by intravenous administration of hematin. 

Estanislao L, Tliomas D, Simpson D (2004) HIV neuromuscular disease and mitochondrial funcdon. Mitochondrion 4 131—139. 

Although moderate consumption of ethanol has health benefits, excessive intake causes disease. Ethanol is rapidly metabohsed by alcohol dehydrogenase in the cytosol to form acetaldehyde. This requires the coenzyme NAD which is reduced to NADH and results in a high ratio of NADH NAD in the cytosol. Subsequently, acetaldehyde is transported into the mitochondrion where it is oxidised by acetaldehyde dehydrogenase to acetate, which results in a high mitochondrial ratio of NADH NAD. This elevation of NADH NAD ratios causes the following metabohc consequences of ethanol abuse. 

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