INFLUENCE OF [DIMETHYLPHOSPHINYLMETHYL)AMINO](PHENYL)-METHYLPHOSPHONIC ACID ON ATPase ACTIVITY OF RAT LIVER MITOCHONDRIA
Keywords:
α-aminophosphonic acids, dimethylphosphinyl-substituted phosphonates, mitochondria, submitochondrial particles, mitochondrial ATPaseAbstract
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.
References
Boyer, P. D., 1997. The ATP synthase – a splendid molecular machine. Ann. Rev. Biochem., 66: 717–749.
Chykaliuk, P., J. Abernathy and J. Gipson, 1980. Bibliography of glyphosate. The Texas Agricultural Experimental Station, Lubbock.
Fiscke, C. H. and Y. Subbarow, 1925. The colorimetric determination of phosphorus. J. Biol. Chem., 66: 375–381.
Hudson, H. R., 2000. Aminophosphonic and Aminophosphinic Acids and their Derivatives as Agrochemicals. 13th chapter in: V. P. Kukhar and H. R. Hudson (Editors), Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity, John Wiley & Sons, Chichester-Toronto, pp. 443–482.
Kafarski, P. and B. Lejczak, 2000. The Biological Activity of Phosphono- and Phosphinopeptides. 12th chapter in: V. P. Kukhar and H. R. Hudson (Editors), Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity, John Wiley & Sons, Chichester-Toronto, pp. 407–442.
Kafarski, P. and B. Lejczak, 2001. Aminophosphonic acids of potential medical importance. Curr. Med. Chem. Anticancer Agents, 1: 301–312.
Lolas, P. and H. Coble, 2006. Translocation of 14C-glyphosate in johnsongrass (Sorghum halepense L. Pers.) as affected by growth stage and rhizome length. Weed Res., 20 (5): 267–270.
Mastalerz, P. and P. Kafarski, 2000. Naturally Occuring Aminophosphonic and Aminophosphinic Acids. 1st chapter in: V. P. Kukhar and H. R. Hudson (Editors), Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity, John Wiley & Sons, Chichester-Toronto, pp. 1–32.
Naydenova, E. D., P. T. Todorov and K. D. Troev, 2010. Recent synthesis of aminophosphonic acids as potential biological importance. Amino Acids, 38: 23–30.
Naydenova, E., K. Troev, M. Topashka-Ancheva, G. Haegele, I. Ivanov and A. Kril, 2007. Synthesis, cytotoxicity and clastogenicity of novel α-aminophosphonic acids. Amino Acids, 33: 695–702.
Naylor, R., 2002. Weed management handbook, 11th chapter ‘‘Herbicide-resistant weeds’’, 9th edn. Blackwell, Banchory.
Oleksyzsyn, J., 2000. Aminophosphonic and Aminophosphinic Acid Derivatives in the Design of Transition State Analogue Inhibitors: Biomedical Opportunities and Limitations. 15th chapter in: V. P. Kukhar and H. R. Hudson (Editors), Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity, John Wiley & Sons, Chichester-Toronto, pp. 537–558.
Orsini, F., G. Sello and M. Sisti, 2010. Aminophosphonic Acids and Derivatives. Synthesis and Biological Applications. Current Medicinal Chemistry, 17: 264–289.
Peixoto, F., 2005. Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation. Chemosphere, 61: 1115–1122.
Shkodrova, M., M. Chichova, D. Ganchev, I. Sazdova and I. Minkov, 2013. Infl uence of sodium nitroprusside as a donor of nitric oxide on ATPase activity of rat liver mitochondria. Bulg. J. Agricult. Sci., 19: 167–170.
Zagraniarsky, Y., B. Ivanova, K. Nikolov, S. Varbanov and T. Cholakova, 2008. Synthesis of Dimethylphosphinyl-substituted α-Amino(aryl)methylphosphonic Acids and Their Esters, Z. Naturforsch., 63b: 1192–1198.
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