Citreoviridin, a specific inhibitor of the mitochondiral adenosine triphosphatase.
1. Citreoviridin was a potent inhibitor of the soluble mitochondrial ATPase (adenosine triphosphatase) similar to the closely related aurovertins B and D. 2. Citreoviridin inhibited the following mitochondrial energy-linked reactions also: ADP-stimulated respiration in whole mitochondria from ox heart and rat liver; ATP-driven reduction of NAD+ by succinate; ATP-driven NAD transhydrogenase and ATPase from ox heart submitochondrial particles. 3. The dissociation constant (KD) calculated by a simple law-of-mass-action treatment for the citreoviridin--ATPase complex was 0.5--4.2micron for ox-heart mitochondrial preparations and 0.15micron for rat liver mitochondria. 4. Monoacetylation of citreoviridin decreased its inhibitory potency (KD=2--25micron, ox heart; KD=0.7micron, rat liver). Diacetylation greatly decreased the inhibitory potency (KD=60--215micron, ox heart). 5. Hydrogenation of citreoviridin monoacetate diminished its inhibitory potency considerably. 6. No significant enhancement of fluorescence was observed when citreoviridin interacted with the mitochondrial ATPase.
D000085:Acetates; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001313:Aurovertins / Q000031:analogs & derivatives / Q000494:pharmacology*; D002417:Cattle; D005453:Fluorescence; D066298:In Vitro Techniques; D008928:Mitochondria / Q000201:enzymology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D000085:Acetates; D000900:Anti-Bacterial Agents; D001313:Aurovertins; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases; C014416:citreoviridin