Hyperglycemiainduced Process

Fig. 6. Effect of agents that alter mitochondrial metabolism on hyperglycemia-induced ROS formation in bovine aortic endothelial cells. Cells were incubated in 5 mM glucose, 30 mM glucose alone, and 30 mM glucose plus either rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m-chlorophenylhydrazone (CCCP), antisense, uncoupling protein-1 (UCP-1), or manganese superoxide dismutase (Mn-SOD) hemagglutinating virus of Japan (HVJ)-liposomes, and ROS were quantitated. (Reproduced with permission from ref. 111.)

Fig. 6. Effect of agents that alter mitochondrial metabolism on hyperglycemia-induced ROS formation in bovine aortic endothelial cells. Cells were incubated in 5 mM glucose, 30 mM glucose alone, and 30 mM glucose plus either rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m-chlorophenylhydrazone (CCCP), antisense, uncoupling protein-1 (UCP-1), or manganese superoxide dismutase (Mn-SOD) hemagglutinating virus of Japan (HVJ)-liposomes, and ROS were quantitated. (Reproduced with permission from ref. 111.)

of glucose metabolism is helpful. Intracellular glucose oxidation begins with glycolysis in the cytoplasm, which generates NADH and pyruvate. Cytoplasmic NADH can donate reducing equivalents to the mitochondrial electron-transport chain via two shuttle systems, or it can reduce pyruvate to lactate, which exits the cell to provide substrate for hepatic gluconeogenesis. Pyruvate can also be transported into the mitochondria, where it is oxidized by the tricarboxylic acid (TCA) cycle to produce CO2, H2O, four molecules of NADH, and one molecule of FADH2. Mitochondrial NADH and FADH2 provide energy for ATP production via oxidative phosphorylation by the electron-transport chain.

Electron flow through the mitochondrial electron-transport chain is carried out by four inner-membrane-associated enzyme complexes, plus cytochrome-c and the mobile carrier ubiquinone (114). NADH derived from both cytosolic glucose oxidation and mitochondrial TCA cycle activity donates electrons to NADH : ubiquinone oxidoreductase (complex I). Complex I ultimately transfers its electrons to ubiquinone. Ubiquinone can also be reduced by electrons donated from several FADH2-containing dehydrogenases, including succinate : ubiquinone oxidoreductase (complex II) and glycerol-3-phosphate dehydrogenase. Electrons from reduced ubiquinone are then transferred to ubiquinol : cytochrome-c oxidoreductase (complex III) by the ubisemiquinone radical-generating Q cycle (115). Electron transport then proceeds through cytochrome-c, cytochrome-c oxidase (complex IV), and, finally, molecular oxygen.

Electron transfer through complexes I, III, and IV generates a proton gradient that drives ATP synthase (complex V). When the electrochemical potential difference generated by this proton gradient is high, the life of superoxide-generating electron-transport intermediates such as ubisemiquinone is prolonged. There appears to be a threshold value above which superoxide production is markedly increased (116).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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