Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex.
The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-acetylcarnitine at two different doses (30 and 60 mg.kg-1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic "light" and "heavy" ones. In fact, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and alpha-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.
Gorini
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Institute of Pharmacology, Faculty of Science, University of Pavia, Italy.
D'Angelo
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Villa
R F
RF
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology
D000108:Acetylcarnitine; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase