Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Kumamoto 860-0082, Japan.
Biol Pharm Bull. 2010;33(3):379-83. doi: 10.1248/bpb.33.379.
Dihydropyrazine (DHP), which is produced during the Maillard reaction, generates radicals that not only cause breakage of chromosomal DNA leading to mutagenic lesions but also induce oxidative damage to cellular proteins. In the present study, we show that three DHP derivatives, which generated superoxide anions, caused inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). SH-compounds, such as cysteine, dithiothreitol (DTT), 2-mercaptoethanol, 2-mercaptoethylamine, and N-acetyl-cysteine, suppressed the inhibition of GAPDH by DHP in vitro, although the effect of DHP on GAPDH was not reversed by DTT. In addition, DHP-exposed Escherichia coli showed almost unaffected growth on plates containing a rich medium, but poor growth on plates containing M9 synthetic medium with glucose as the sole carbon source. Furthermore, DHP-exposed E. coli exhibited reduced GAPDH activity. These findings indicate that DHP disturbs the glycolytic pathway by inhibiting GAPDH activity.
二氢吡嗪（DHP）是美拉德反应的产物，会产生自由基，不仅导致染色体 DNA 断裂引发致突变损伤，还会诱导细胞蛋白质发生氧化损伤。在本研究中，我们发现三种能够产生超氧阴离子的 DHP 衍生物会抑制甘油醛-3-磷酸脱氢酶（GAPDH）。巯基化合物，如半胱氨酸、二硫苏糖醇（DTT）、2-巯基乙醇、2-巯基乙胺和 N-乙酰半胱氨酸，能够抑制 DHP 在体外对 GAPDH 的抑制作用，但 DTT 并不能逆转 DHP 对 GAPDH 的抑制作用。此外，DHP 暴露的大肠杆菌在含有丰富培养基的平板上的生长几乎不受影响，但在含有以葡萄糖为唯一碳源的 M9 合成培养基的平板上的生长较差。此外，DHP 暴露的大肠杆菌的 GAPDH 活性降低。这些发现表明，DHP 通过抑制 GAPDH 活性干扰糖酵解途径。
