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.
Gerber
E
E
Institute of Toxicology, University of Düsseldorf, Germany.
Bredy
A
A
Kahl
R
R
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D042963:Electron Transport Complex II; D004734:Energy Metabolism / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007502:Iron Chelating Agents / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010618:Phenanthrolines / Q000633:toxicity*; D011480:Protease Inhibitors / Q000633:toxicity*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
D007502:Iron Chelating Agents; D009097:Multienzyme Complexes; D010618:Phenanthrolines; D011480:Protease Inhibitors; D011773:Pyruvates; D017382:Reactive Oxygen Species; D002245:Carbon Dioxide; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D005993:Glycerolphosphate Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D000251:Adenosine Triphosphatases; D005990:Glycerol; C025205:1,10-phenanthroline