Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, CEP 90035-003 Porto Alegre, RS, Brazil.
Food Chem Toxicol. 2012 Oct;50(10):3468-74. doi: 10.1016/j.fct.2012.07.049. Epub 2012 Aug 1.
Tellurium has been used as an industrial component of many alloys and in the electronic industry. Organotellurium compounds can cause poisoning which leads to neurotoxic symptoms such as significant impairment of learning, spatial memory and are potentially neurotoxic to human beings. However, the molecular mechanisms of neurotoxicity of organotellurium compounds are not well understood. Considering that creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue, the main objective of this study was to investigate the mechanisms by which 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one inhibit creatine kinase activity, a key enzyme of energy homeostasis, in the cerebral cortex of 30-day-old Wistar rats. For the kinetic studies, the Lineweaver-Burk plot was used to characterize the mechanisms of enzyme inhibition by 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one. The results suggested that this compound inhibits creatine kinase activity by two different mechanisms: competition with ADP and oxidation of critical sulfhydryl groups for the functioning of the enzyme. The potential for inhibition of creatine kinase to occur in vivo may contribute to the neurotoxicity observed by this organochaocogen.
碲已被用作许多合金的工业成分和电子工业。有机碲化合物可引起中毒，导致神经毒性症状，如学习能力显著受损、空间记忆受损，对人类有潜在的神经毒性。然而，有机碲化合物的神经毒性的分子机制还不是很清楚。考虑到肌酸激酶在具有间歇性高且波动的能量需求的组织（如神经组织）的能量代谢中发挥着关键作用，本研究的主要目的是研究 3-丁基-1-苯基-2-(苯基碲)辛-1-酮抑制 30 日龄 Wistar 大鼠大脑皮层肌酸激酶活性的机制，肌酸激酶是能量稳态的关键酶。对于动力学研究，采用 Lineweaver-Burk 作图来表征 3-丁基-1-苯基-2-(苯基碲)辛-1-酮对酶抑制的机制。结果表明，该化合物通过两种不同的机制抑制肌酸激酶活性：与 ADP 的竞争和氧化关键巯基基团以维持酶的功能。肌酸激酶抑制作用在体内发生的可能性可能导致了这种有机硫代锗化合物观察到的神经毒性。
