INFLUENCE OF DIMETHYLPHOSPHINYLMETHYL)AMINO(PHENYL)-METHYLPHOSPHONIC ACID ON ATPase ACTIVITY OF RAT LIVER MITOCHONDRIA
Ts. Cholakova, D. Donchevastoimenova, H. Dimov, M. Shkodrova, S. Varbanov, Y. Zagraniarsky, D. Ganchev, M. Vydevska-Chichova
Abstract: Extensive studies on biological activity of α-aminophosphonic acids have been carried out because of their structural analogy with α-aminocarboxylic acids. Several α-aminophosphonic acid derivatives such as glyphosate, the fundamental substance of the herbicide Roundup, are widely used commercially. [(Dimethylphosphinylmethyl)amino](phenyl)-methylphosphonic acid (DMPPA) is an
original α-aminophosphonic acid with dimethylphosphinyl substituent in the molecule. Its preparation has been reported recently. The knowledge of these types of α-aminophosphonic acids is scarce although its molecular structure might determine potential biological activity. The present work was undertaken to investigate the influence of DMPPA on ATPase activity of rat liver mitochondria. Three different mitochondrial preparations were used: intact mitochondria, mitochondria uncoupled by freezing/thawing and submitochondrial
particles (SMPs). ATPase activity was determined by measurement of the inorganic phosphate increase in the reaction medium. Two approaches were applied to examine the effects of DMPPA on the ATPase activity of uncoupled mitochondria and SMPs. A set of experiments was conducted under conditions allowing simultaneous interactions of the substrate ATP and DMPPA with the active site of the enzyme. The second approach enabled to study the influence of DMPPA under conditions providing its interaction with the active site prior to saturation with the substrate. We found that DMPPA did not infl uence ATPase activity of both intact and 2,4-dinitrophenol-uncoupled mitochondria. This suggests that DMPPA does not possess uncoupling effect on intact liver mitochondria and is
not able to pass the inner mitochondrial membrane. DMPPA inhibited ATPase activity of both freeze/thawed mitochondria and SMPs. These effects were demonstrated by both approaches of study. It is concluded that DMPPA effects on the ATPase activity of uncoupled mitochondria and SMPs are most probably due to direct interactions of the compound with the enzyme. This study provides a better insight into the mechanisms of the potential biological activity of the α-aminophosphonic acids and theirs derivatives.
original α-aminophosphonic acid with dimethylphosphinyl substituent in the molecule. Its preparation has been reported recently. The knowledge of these types of α-aminophosphonic acids is scarce although its molecular structure might determine potential biological activity. The present work was undertaken to investigate the influence of DMPPA on ATPase activity of rat liver mitochondria. Three different mitochondrial preparations were used: intact mitochondria, mitochondria uncoupled by freezing/thawing and submitochondrial
particles (SMPs). ATPase activity was determined by measurement of the inorganic phosphate increase in the reaction medium. Two approaches were applied to examine the effects of DMPPA on the ATPase activity of uncoupled mitochondria and SMPs. A set of experiments was conducted under conditions allowing simultaneous interactions of the substrate ATP and DMPPA with the active site of the enzyme. The second approach enabled to study the influence of DMPPA under conditions providing its interaction with the active site prior to saturation with the substrate. We found that DMPPA did not infl uence ATPase activity of both intact and 2,4-dinitrophenol-uncoupled mitochondria. This suggests that DMPPA does not possess uncoupling effect on intact liver mitochondria and is
not able to pass the inner mitochondrial membrane. DMPPA inhibited ATPase activity of both freeze/thawed mitochondria and SMPs. These effects were demonstrated by both approaches of study. It is concluded that DMPPA effects on the ATPase activity of uncoupled mitochondria and SMPs are most probably due to direct interactions of the compound with the enzyme. This study provides a better insight into the mechanisms of the potential biological activity of the α-aminophosphonic acids and theirs derivatives.
Keywords: dimethylphosphinyl-substituted phosphonates; mitochondria; mitochondrial ATPase; submitochondrial particles; α-aminophosphonic acids
Date published: 2017-10-18
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