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the above collected data provide new insights to understand the participation of lactate and citrate in brain energy metabolism and in the repair of injured tissue. the lactate-citrate shuttle and the cytosolic lactate dehydrogenase (cytldh) generates intermediates for oxidative phosphorylation in the mitochondrial matrix and at the inner mitochondrial membrane. the cytldh catalyses the conversion of lactate to pyruvate in the cytosol by transferring electrons to ubiquinone, which then passes them onto the mitochondrial respiratory chain. cell swelling, metabolic stress and ischemia are the major causes for increased cytosolic lactate accumulation, which affects recovery and survival of cells. thus, understanding the metabolism of lactate and citrate in the brain could contribute to the development of new therapeutic strategies for severe brain injuries or stroke. as far as the citric acid cycle is concerned, the reduction of mitochondrial metabolism in the brain and the increase of its dependence on extramitochondrial fuels can have a metabolic role in the progression of certain neurological disorders, and a therapeutic role in brain injury conditions. this study also showed the existence of specific regulatory mechanisms for the lactate-citrate shuttle across the blood-brain barrier and opens new perspectives to better understand the role of this shuttle in the pathogenesis of brain diseases.
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a natural isolate nocardiopsis halophila a3(t), in which two fumarate reductases were heterologously expressed, was able to produce succinic acid, fumaric acid and malic acid simultaneously. this method also allows for an easy removal of succinic acid from the reaction mixture, ensuring an accumulation of the other desired products. we obtained a succinic acid yield of 60%.