Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Toxicol In Vitro. 2010 Apr;24(3):1045-51. doi: 10.1016/j.tiv.2009.11.012. Epub 2009 Nov 16.
Lead intoxication is a serious occupational disease that constitutes a major public health problem. Lead, a heavy metal, has been used by humans for many technological purposes, which is the main reason for its widespread distribution. The toxic mechanisms of lead on the molecular machinery of living organisms include metal transport, energy metabolism, diverse enzymatic processes, genetic regulation, and membrane ionic channels and signaling molecules. Since lead is able to cross the blood-brain barrier it may cause neurotoxicity. Creatine kinase and pyruvate kinase are two thiol-containing enzymes that exert a key role for cellular energy homeostasis in brain. Our main objective was to investigate the in vitro effect of lead on pyruvate kinase and creatine kinase activities of extracts and subcellular fractions from the brain cortex of rats in the presence or not of thiol-protecting substances such as glutathione and cysteamine. The results showed that lead inhibited the two enzyme activities and the thiol-protecting substances prevented their inhibition. These results suggest that lead inhibits creatine kinase and pyruvate kinase activity by interaction with their thiol groups. Therefore, lead may disrupt energy homeostasis and this effect may contribute to the neurological dysfunction found in lead exposed individuals.
铅中毒是一种严重的职业病，构成了一个主要的公共卫生问题。铅是一种重金属，人类已经将其用于许多技术用途，这是其广泛分布的主要原因。铅对生物分子机制的毒性机制包括金属转运、能量代谢、多种酶过程、遗传调控以及膜离子通道和信号分子。由于铅能够穿过血脑屏障，因此它可能导致神经毒性。肌酸激酶和丙酮酸激酶是两种含巯基的酶，在大脑细胞能量稳态中发挥关键作用。我们的主要目的是研究铅在存在或不存在巯基保护物质（如谷胱甘肽和半胱胺）的情况下，对大鼠大脑皮质提取物和亚细胞级分中丙酮酸激酶和肌酸激酶活性的体外影响。结果表明，铅抑制了这两种酶的活性，而巯基保护物质则阻止了它们的抑制。这些结果表明，铅通过与它们的巯基相互作用抑制肌酸激酶和丙酮酸激酶的活性。因此，铅可能会破坏能量稳态，这种作用可能导致暴露于铅的个体中发现的神经功能障碍。
