Eisenbrand G, Schuhmacher J, Gölzer P
Department of Chemistry, Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Germany.
Chem Res Toxicol. 1995 Jan-Feb;8(1):40-6. doi: 10.1021/tx00043a005.
The reaction of 2-alkenals with GSH to form GSH conjugates by Michael addition is a major detoxification pathway. The reaction proceeds at a much higher rate under catalysis by glutathione S-transferase (GST) than the non-enzymatic reaction. Oxidation of 2-alkenals to the corresponding acids by cytosolic and microsomal fraction of rat liver also contributes to detoxification. Primary rat hepatocytes rich in GSH and proficient for GST and other metabolizing enzymes consume much more alkenal than human lymphoblastoid cells (Namalva cells), that are poor in GSH and in metabolic activities. In Namalva cells DNA single strand breaks were induced by much lower concentrations of acrolein, crotonaldehyde and (E)-2-hexenal than in primary rat hepatocytes. In both cell systems intracellular GSH depletion by 2-alkenals proceeds in a dose dependent manner, approaching about 20% of pretreatment level before DNA damage becomes detectable. GSH conjugates of (E)-2-hexenal and (2E,6Z)-2,6-nonadienal induce DNA damage in Namalva cells at high concentrations (1.5 mM). In the absence of GSH these conjugates decompose slowly into aldehyde and GSH. Although the rate of decomposition is only about 10(-4) times that of Michael adduct formation, such GSH conjugates could potentially function as transport molecules for 2-alkenals, if they reach tissues low in GSH and GST.
2-烯醛与谷胱甘肽（GSH）通过迈克尔加成反应形成GSH共轭物是一条主要的解毒途径。该反应在谷胱甘肽S-转移酶（GST）催化下比非酶促反应进行得快得多。大鼠肝脏胞液和微粒体部分将2-烯醛氧化为相应的酸也有助于解毒。富含GSH且具有高效GST和其他代谢酶的原代大鼠肝细胞比GSH和代谢活性较低的人淋巴母细胞（Namalva细胞）消耗更多的烯醛。在Namalva细胞中，与原代大鼠肝细胞相比，更低浓度的丙烯醛、巴豆醛和（E）-2-己烯醛就能诱导DNA单链断裂。在这两种细胞系统中，2-烯醛导致的细胞内GSH消耗呈剂量依赖性，在DNA损伤可检测到之前，GSH消耗接近预处理水平的20%左右。（E）-2-己烯醛和（2E,6Z）-2,6-壬二烯醛的GSH共轭物在高浓度（1.5 mM）时可诱导Namalva细胞中的DNA损伤。在没有GSH的情况下，这些共轭物会缓慢分解为醛和GSH。尽管分解速率仅约为迈克尔加成物形成速率的10^(-4)倍，但如果这些GSH共轭物到达GSH和GST含量较低的组织，它们可能潜在地作为2-烯醛的转运分子发挥作用。
