Influence of [Dimethylphosphinylmethyl)Amino](Phenyl)-Methylphosphonic Acid on Atpase Activity of Rat Liver Mitochondria

1 University of Sofia “St. Kliment Ohridski”, Department of Animal and Human Physiology, Faculty of Biology, BG – 1164 Sofia, Bulgaria
2 University of Sofia “St. Kliment Ohridski”, Department of Organic Chemistry, Faculty of Chemistry and Pharmacy, BG – 1164 Sofia, Bulgaria
3 Bulgarian Academy of Sciences, Institute of Organic Chemistry with Center of Phytochemistry, BG – 1113 Sofia, Bulgaria


SHKODROVA, M., M. VYDEVSKA-CHICHOVA, H. DIMOV, D. GANCHEV, D. DONCHEVA-STOIMENOVA, Y. ZAGRANIARSKY, Ts. CHOLAKOVA and S. VARBANOV, 2014. Infl uence of [Dimethylphosphinylmethyl)amino] (phenyl)-methylphosphonic acid on ATPase activity of rat liver mitochondria. Bulg. J. Agric. Sci., Supplement 1: 9–14

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 infl uence 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 infl uence 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.

Key words: α-aminophosphonic acids, dimethylphosphinyl-substituted phosphonates, mitochondria, submitochondrial particles, mitochondrial ATPase
Abbreviations: ATP – adenosine triphosphate; ATPase – adenosine triphosphatase; DMPPA – [(Dimethylphosphinylmethyl)amino](phenyl)-methylphosphonic acid; DNP – 2,4-dinitrophenol; Pi – inorganic phosphate; SMPs – submitochondrial particles


See the article as a PDF.