A comparison of the effects of NN'-dicyclohexylcarbodi-imide, oligomycin A and aurovertin on enrgy-linked reactions in mitochondria and submitochondrial particles.
1. The effects of dicyclohexylcarbodi-imide, oligomycin A and aurovertin on enzyme systems related to respiratory-chain phosphorylation were compared. Dicyclohexylcarbodi-imide and oligomycin A have very similar functional effects, giving 50% inhibition of ATP-utilizing and ATP-generating systems at concentrations below 0.8nmole/mg. of submitochondrial-particle protein. Aurovertin is a more potent inhibitor of ATP synthesis, giving 50% inhibition at 0.2nmole/mg. of protein. However, aurovertin is a less potent inhibitor of ATP-utilizing systems: the ATP-driven energy-linked nicotinamide nucleotide transhydrogenase is 50% inhibited at 3.0nmoles/mg. of protein and the ATP-driven reduction of NAD(+) by succinate is 50% inhibited at 0.95nmole/mg. of protein. 2. With EDTA-particles (prepared by subjecting mitochondria to ultrasonic radiation at pH9 in the presence of 2mm-EDTA) the maximum stimulation of the ATP-driven partial reactions is effected by similar concentrations of oligomycin A and dicylcohexylcarbodi-imide, but the latter is less effective. The stimulatory effects of suboptimum concentrations of dicyclohexylcarbodi-imide and oligomycin A are additive. Aurovertin does not stimulate these reactions or interfere with the stimulation by the other inhibitors. 3. Dicyclohexylcarbodi-imide and oligomycin A stimulate the aerobic energy-linked nicotinamide nucleotide transhydrogenase of EDTA-particles, but the optimum concentration is higher than that required for the ATP-driven partial reactions. Aurovertin has no effect on this reaction. 4. The site of action of dicyclohexylcarbodi-imide is in CF(0), the mitochondrial fraction that confers oligomycin sensitivity on F(1) mitochondrial adenosine triphosphatase.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002417:Cattle; D003510:Cyclohexanes; D003580:Cytochromes; D003864:Depression, Chemical; D004492:Edetic Acid / Q000494:pharmacology; D004735:Energy Transfer; D006321:Heart / Q000187:drug effects; D007094:Imides / Q000494:pharmacology*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D013386:Succinates
D000227:Adenine Nucleotides; D000963:Antimetabolites; D003510:Cyclohexanes; D003580:Cytochromes; D007094:Imides; D009840:Oligomycins; D013386:Succinates; D009243:NAD; D004492:Edetic Acid; D000251:Adenosine Triphosphatases