Phenylethynyl-Butyltellurium Inhibits the Sulfhydryl Enzyme Na+, K+-ATPase: An Effect Dependent on the Tellurium Atom
- 187 Downloads
Organotellurium compounds are known for their toxicological effects. These effects may be associated with the chemical structure of these compounds and the oxidation state of the tellurium atom. In this context, 2-phenylethynyl-butyltellurium (PEBT) inhibits the activity of the sulfhydryl enzyme, δ-aminolevulinate dehydratase. The present study investigated on the importance of the tellurium atom in the PEBT ability to oxidize mono- and dithiols of low molecular weight and sulfhydryl enzymes in vitro. PEBT, at high micromolar concentrations, oxidized dithiothreitol (DTT) and inhibited cerebral Na+, K+-ATPase activity, but did not alter the lactate dehydrogenase activity. The inhibition of cerebral Na+, K+-ATPase activity was completely restored by DTT. By contrast, 2-phenylethynyl-butyl, a molecule without the tellurium atom, neither oxidized DTT nor altered the Na+, K+-ATPase activity. In conclusion, the tellurium atom of PEBT is crucial for the catalytic oxidation of sulfhydryl groups from thiols of low molecular weight and from Na+, K+-ATPase.
KeywordsTellurium Sulfhydryl enzymes Thiol Toxicity Na+, K+-ATPase
The financial support by UFSM, CAPES, FAPERGS/CNPq (PRONEX) (research grant no. 10/0005-1) and FAPERGS (no. 10/0711-6) is gratefully acknowledged. C.W.N is a recipient of CNPq fellowship.
- 2.Petragnani N (1995) In: Comprehensive organometallic chemistry II (Ed. A. Mckillop), vol. LI, Pergamon, Exeter.Google Scholar
- 5.Comparsi B, Meinerz DF, Franco JL, Posser T, Prestes AS, Stefanello ST, Santos DB, Wagner C, Farina M, Aschner M, Dafre AL, Rocha JBT (2012) Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. Mol Cell Biochem 370:173–182PubMedCrossRefGoogle Scholar
- 6.Heimfarth LL, Samanta O, Reis KP, Lima BO, Zamboni F, Lacerda S, Soska AK, Wild L, Rocha JBT, Pessoa-Pureur R (2012) Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats. Arch Toxicol 86:217–230PubMedCrossRefGoogle Scholar
- 9.Nogueira CW, Rocha JBT (2012) The chemistry of organic selenium and tellurium compounds. In: Rappport Z (ed) Patai’s chemistry of functional groups. Wiley, New York, pp 1277–1357Google Scholar
- 15.Fiske CH, Subbarows YJ (1925) The calorimetric determination of phosphorus. Biol Chem 66:375–381Google Scholar
- 16.Pereira ME, Borignon AM, Burger C (1991) Long-term treatment with 2,5-hexaedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adults rats. Bras J Med Biol 24:735–740Google Scholar
- 25.Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, David W, Jonathan W, Jon W, Kevin H (2012) Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation. J Med Chem 55:3285–3306PubMedCrossRefGoogle Scholar
- 26.Phillips D, Blake CCF, Watson HC (1981) The enzymes of glycolysis: structure, activity, and evolution. Philos Trans R Soc Lond B Biol Sci 293:1–214Google Scholar