Thiamine induces long-term changes in amino acid profiles and activities of 2-oxoglutarate and 2-oxoadipate dehydrogenases in rat brain
- Authors: Tsepkova P.M.1, Artiukhov A.V.1, Boyko A.I.1, Aleshin V.A.1, Mkrtchyan G.V.1, Zvyagintseva M.A.2, Ryabov S.I.2, Ksenofontov A.L.3, Baratova L.A.3, Graf A.V.4,5, Bunik V.I.1,3
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Affiliations:
- Faculty of Bioengineering and Bioinformatics
- Russian Cardiology Research-and-Production Complex
- Belozersky Institute of Physico-Chemical Biology
- Faculty of Biology
- Faculty of Nano-, Bio-, Informational, and Cognitive Technologies
- Issue: Vol 82, No 6 (2017)
- Pages: 723-736
- Section: Review
- URL: https://journals.rcsi.science/0006-2979/article/view/151415
- DOI: https://doi.org/10.1134/S0006297917060098
- ID: 151415
Cite item
Abstract
Molecular mechanisms of long-term changes in brain metabolism after thiamine administration (single i.p. injection, 400 mg/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 dehydrogenases. 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 (i) the brain-region-specific alterations of glutamine synthase and/or glutamate dehydrogenase and NADP+-dependent malic enzyme, (ii) the brain-region-specific changes of the amino acid profiles, and (iii) decreased levels of a number of 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 analysis of correlations between the levels of amino acids. The set and parameters of the correlations were tissue-specific, and their responses to the 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 catabolism of amino acids by means of a 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.
About the authors
P. M. Tsepkova
Faculty of Bioengineering and Bioinformatics
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234
A. V. Artiukhov
Faculty of Bioengineering and Bioinformatics
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234
A. I. Boyko
Faculty of Bioengineering and Bioinformatics
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234
V. A. Aleshin
Faculty of Bioengineering and Bioinformatics
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234
G. V. Mkrtchyan
Faculty of Bioengineering and Bioinformatics
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234
M. A. Zvyagintseva
Russian Cardiology Research-and-Production Complex
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 121552
S. I. Ryabov
Russian Cardiology Research-and-Production Complex
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 121552
A. L. Ksenofontov
Belozersky Institute of Physico-Chemical Biology
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119991
L. A. Baratova
Belozersky Institute of Physico-Chemical Biology
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119991
A. V. Graf
Faculty of Biology; Faculty of Nano-, Bio-, Informational, and Cognitive Technologies
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119991; Moscow, 123098
V. I. Bunik
Faculty of Bioengineering and Bioinformatics; Belozersky Institute of Physico-Chemical Biology
Author for correspondence.
Email: bunik@belozersky.msu.ru
Russian Federation, Moscow, 119234; Moscow, 119991