ピリジンカルボン酸遷移金属複合体による活性酸素の生成

抄録

1. Pyridine compounds with 2-carboxylic group produced reactive oxygen species in the presence of transition metals, iron and copper. Aconitase, the most sensitive enzyme to oxidative stress was inactivated markedly by dipicolinic acid (pyridine 2, 6-dicarboxylic acid) and less potently by picolinic acid (pyridine 2-carboxylic acid) in the presence of ferrous sulfate. The inactivation was dependent on KCN, an inhibitor of Cu/Zn-SOD, suggesting that pyridine carboxylate/iron complexes can generate superoxide radical as a principal product. Introduction of carboxylic groups to 3, 4 or 5 in the pyridine ring decreased the inactivating effect. 2. Aconitase was also inactivated by copper/ascorbate complex, particularly in the presence of pyridine 2, 4-dicarboxylic acid (lutidinic acid). The inactivation was dependent on sodium azide, an inhibitor of catalase, suggesting that Cu/ascorbate produces hydrogen peroxide. 3. Dipicolinic acid and lutidinic acid at lower concentrations enhanced the Cu/ascorbate-dependent formation of 8-hydroxy-2’-deoxyguanosine in DNA, indicating generation of hydroxyl radical. Prooxidant action of pyridine carboxylic acids may explain the bactericidal or apoptotic action of these compounds reported previously.