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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 18, Art. 2 (pp. 50-80)    |    2017       
»

Biochemical basics of fumarate-containing medicines action
Maevsky E.I.1,2, Grishina E.V.1

1)Institute if theoretical and experimental biophysics of Russian academy of sciences. Pushchino, Moscow region, Russia.
2)Institute of Engineering Physics. Serpukhov, Moscow region, Russia.



Brief summary

The review analyzes literature data on the clinical use of the fumarate-containing medicines injected intravenously in intensive care, and materials of authors' research on the biochemical transformations of fumarate in animals and humans. The use of high doses of the fumarate-containing medicines (about 30 g with a single administration) indicates a high safety of sodium fumarate. Metabolic transformations of fumarate providing under aerobic conditions maintenance of blood glucose level, complete oxidation of fatty acids and mitochondrial-cytosolic transport of reducing equivalents are considered. The NADH fumarate reductase reaction plays a key role in the anaerobic formation of succinate and in maintaining the energy status of mitochondria and cells during hypoxia. The authors analyze not only the "fuel" role of fumarate in the energy of the cell, but also the fumarate participation in signal reactions associated with activation of the succinate receptor and stabilization of the cytosolic hypoxia-inducible factor (HIF). Attention is focused on the participation of the NADH fumarate reductase reaction in physiological adaptation to hypoxia and in hypoxia-like "adaptation" of neoplasms. The feasibility of using small doses of fumarate in the composition of biologically active additives has been postulated.


Key words

fumarate-containing medicines, fumarate metabolism, aerobic and anaerobic conditions, anaerobic succinate formation, hypoxic adaptation





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