Thiamine induces long-term changes in amino acid profiles and activities of 2-oxoglutarate and 2-oxoadipate dehydrogenases in rat brainстатья

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1. Полный текст Tsepkova2017_Article_ThiamineInducesLong-termChange.pdf 602,4 КБ 7 сентября 2018 [feniouk]

[1] Thiamine induces long-term changes in amino acid profiles and activities of 2-oxoglutarate and 2-oxoadipate dehydrogenases in rat brain / P. M. Tsepkova, A. V. Artiukhov, A. I. Boyko et al. // Biochemistry (Moscow). — 2017. — Vol. 82, no. 6. — P. 723–736. Molecular mechanisms of long term changes in brain metabolism after thiamine administration (single i.p. injection, 400 mg per kg) were investigated. Protocols for discrimination of the activities of the thiamine diphosphate (ThDP) dependent 2 oxoglutarate and 2 oxoadipate dehydrogenases were developed to characterize specific regulation of the multienzyme complexes of the 2 oxoglutarate (OGDHC) and 2 oxoadipate (OADHC) dehydrogenases by thiamine. The thiamine induced changes depended on the brain region specific expression of the ThDP dependent dehydro genases. In the cerebral cortex, the original levels of OGDHC and OADHC were relatively high and not increased by thiamine, whereas in the cerebellum thiamine upregulated the OGDHC and OADHC activities whose original levels were relatively low. The effects of thiamine on each of the complexes were different and associated with metabolic rearrangements, which included (1) brain region specific alterations of glutamine synthase and/or glutamate dehy drogenase and NADP+ dependent malic enzyme, (2) brain region specific changes in the amino acid profiles, and (3) decreased levels of several amino acids in blood plasma. Along with the assays of enzymatic activities and average levels of amino acids in the blood and brain, the thiamine induced metabolic rearrangements were assessed by the analysis of correlations between the levels of amino acids. The set and parameters of the correlations were tissue spe cific, and their responses to thiamine treatment provided additional information on metabolic changes compared to that gained from the average levels of amino acids. Taken together, the data suggest that thiamine decreases catabo lism of amino acids by means of complex and long term regulation of metabolic flux through the tricarboxylic acid cycle, which includes coupled changes in activities of the ThDP dependent dehydrogenases of 2 oxoglutarate and 2 oxoadipate and adjacent enzymes. [ DOI ]

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