Instituto de Ciências da Saúde, Grupo de Pesquisa em Bioanálise, Universidade Feevale, RS 239, 2755, Novo Hamburgo, RS CEP 93352-000, Brazil.
Arch Environ Contam Toxicol. 2012 Oct;63(3):453-60. doi: 10.1007/s00244-012-9786-z. Epub 2012 Aug 5.
Lead (Pb(2+)) is a heavy metal that has long been used by humans for a wide range of technological purposes, which is the main reason for its current widespread distribution. Pb(2+) is thought to enter erythrocytes through anion exchange and to remain in the cell by binding to thiol groups. Pyruvate kinase (PK) is a thiol-containing enzyme that plays a key role in erythrocyte cellular energy homeostasis. δ-aminolevulinic acid dehydratase (δ-ALAD) is the second enzyme in the heme biosynthetic pathway and plays a role in the pathogenesis of Pb poisoning. Our primary objective was to investigate the effect of Pb(2+) on the activity of the thiolenzymes δ-ALAD and PK and on the concentration of glutathione (GSH), a nonenzymatic antioxidant defense, in erythrocytes from Pb-exposed workers. The study sample comprised 22 male Pb workers and 21 normal volunteers (15 men and 6 women). The Pb-exposed workers were employed in manufacturing and recycling of automotive batteries. Basic red-cell parameters were assayed and total white blood cell counts performed. PK and δ-ALAD activity and blood Pb (BPb) concentrations were determined in all subjects. Pb-exposed individuals had significantly greater BPb levels than controls. Both PK and δ-ALAD activity levels were significantly lower in Pb-exposed individuals than in controls. Pb significantly inhibited PK and δ-ALAD activity in a dose-dependent manner. We found that erythrocyte GSH levels were lower in Pb-exposed individuals than normal volunteers. Pb-exposed individuals had lower values than controls for several red cell parameters (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume). These results suggest that Pb inhibits δ-ALAD and PK activity by interacting with their thiol groups. It is therefore possible that Pb disrupts energy homeostasis and may be linked with decreased glucose metabolism because it affects the heme synthesis pathway in erythrocytes, contributing to the cell dysfunction observed in these in Pb-exposed individuals. These results indicate an apparent dose-effect relationship between PK activity and BPb. PK activity in human erythrocytes can be used for biological monitoring of Pb exposure. Study of the mechanisms by which Pb acts may contribute to greater understanding of the symptoms caused by Pb.
铅（Pb(2+)）是一种重金属，长期以来一直被人类广泛用于各种技术用途，这也是其目前广泛分布的主要原因。人们认为 Pb(2+) 通过阴离子交换进入红细胞，并通过与巯基结合而留在细胞内。丙酮酸激酶（PK）是一种含巯基的酶，在红细胞细胞能量稳态中发挥关键作用。δ-氨基酮戊酸脱水酶（δ-ALAD）是血红素生物合成途径中的第二种酶，在 Pb 中毒的发病机制中起作用。我们的主要目的是研究 Pb(2+) 对含巯基酶 δ-ALAD 和 PK 的活性以及红细胞中谷胱甘肽（GSH）浓度（一种非酶抗氧化防御）的影响，这些工人曾暴露于 Pb 之下。研究样本包括 22 名男性 Pb 工人和 21 名正常志愿者（15 名男性和 6 名女性）。暴露于 Pb 的工人从事汽车电池的制造和回收工作。测定了基本的红细胞参数，并进行了白细胞总数计数。在所有受试者中测定了 PK 和 δ-ALAD 活性以及血 Pb（BPb）浓度。暴露于 Pb 的个体的 BPb 水平明显高于对照组。暴露于 Pb 的个体的 PK 和 δ-ALAD 活性水平明显低于对照组。Pb 以剂量依赖性方式显著抑制 PK 和 δ-ALAD 活性。我们发现暴露于 Pb 的个体的红细胞 GSH 水平低于正常志愿者。暴露于 Pb 的个体的几个红细胞参数（血红蛋白、红细胞压积、红细胞计数、平均红细胞体积）值低于对照组。这些结果表明，Pb 通过与它们的巯基相互作用抑制 PK 和 δ-ALAD 活性。因此，Pb 可能通过影响红细胞中的血红素合成途径而破坏能量稳态，并与葡萄糖代谢降低有关，从而导致暴露于 Pb 的个体中观察到的细胞功能障碍。这些结果表明 PK 活性与 BPb 之间存在明显的剂量-效应关系。人红细胞中的 PK 活性可用于生物监测 Pb 暴露。对 Pb 作用机制的研究可能有助于更好地了解 Pb 引起的症状。
