Ortho-phenanthroline modulates enzymes of cellular energy metabolism

The lipophilic iron chelator 1,10-phenanthroline has been used in mechanistic studies on intracellular oxidant damage because iron is assumed to play a role in the endogenous formation of highly reactive oxygen species. This study shows that 1,10-phenanthroline has enzyme-modulatory properties in addition to its antioxidant activity. In rat hepatocytes, 1,10-phenanthroline caused inhibition of respiration and enhancement of cellular ATP content, pyruvate release and CO2 formation from glycerol resulting from a modulatory action of 1,10-phenanthroline on various enzymes involved in cellular energy metabolism. In intact mitochondria and in submitochondrial particles, oxygen consumption, complex I activity, and ATPase degradation are inhibited by 1,10-phenanthroline. In submitochondrial particles, complex II activity can also be suppressed by 1,10-phenanthroline. The purified cytosolic enzymes lactate dehydrogenase and glycerol-3-phosphate dehydrogenase are inhibited while purified glyceraldehyde-3-phosphate dehydrogenase is activated by 1,10-phenanthroline. The results suggest that 1,10-phenanthroline modulates various enzyme activities linked to cellular energy metabolism and that this property must be taken into account when using 1,10-phenanthroline as a tool in experiments on oxidant effects in cells.