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Biochemistry Research International
Volume 2013, Article ID 495135, 8 pages
http://dx.doi.org/10.1155/2013/495135
Research Article

Inhibition of Rat Muscle and Liver Phosphofructokinases by High Doses of Ethanol

1Department of Clinical Laboratory Diagnostics, Allergology and Immunology, Grodno State Medical University, Gorkogo 80, 230009 Grodno, Belarus
2Department of General Chemistry, Belarusian State Medical University, Dzerzinskogo 83, 220116 Minsk, Belarus

Received 29 July 2013; Revised 18 September 2013; Accepted 23 September 2013

Academic Editor: Paul W. Doetsch

Copyright © 2013 Sergey Vladimirovich Lelevich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activities of both rat muscle and liver phosphofructokinases are significantly inhibited after a single ethanol intake in the dose of 2.5 g per kg of body weight. This inhibitory effect is indirect, since ethanol in concentration (50 mM) close to that established after 2.5 g per kg of body weight intake cannot decrease their activities in vitro. Inhibition of liver phosphofructokinase activity after the 5.0 g per kg ethanol intake may be direct, since liver phosphofructokinase activity decreases in vitro when ethanol is added to supernatants of rat liver tissue in 100 mM concentration. According to the results of molecular docking, ethanol at high concentrations can be bound by adenine-binding pocket of the allosteric ADP-binding site of liver phosphofructokinase (Asp543, Phe308, Phe538, and Phe671) and its activation by ADP can be blocked by C2H5OH molecule. Direct inhibition of muscle phosphofructokinase activity, probably due to the binding of ethanol to the similar ADP-binding site, is possible when the concentration of ethanol (500 mM) is much higher than the level which can be established in living cells. So, inhibition of muscle phosphofructokinase activity after a single 5.0 g per kg intake is indirect and probably linked with the inhibition of the enzyme by elevated citrate and phosphoenolpyruvate levels.