On the mechanism of maleate action on rat kidney mitochondria. Effect on substrate-level phosphorylation.
1. Maleate inhibits the substrate-level phosphorylation linked to anaerobic dismutation of 2-oxoglutarate in rat kidney mitochondria. 2. Phosphate and magnesium diminish the inhibitory effect of maleate. Arsenate also relieves the inhibition of 2-oxoglutarate consumption but only at low (1 mM) phosphate concentration; at higher concentrations, the action of phosphate and arsenate is competitive. 3. Acetoacetate, malonate and succinate, the substrates of CoA-transferase, relieve the inhibition of 2-oxoglutarate metabolism by maleate both in the respiring mitochondria and in the "anaerobic" system containing antimycin and rotenone. 4. The interference in succinyl-CoA metabolism by maleate is discussed as a possible mechanism of the inhibitory action of this compound.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001151:Arsenic / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008298:Maleates / Q000494:pharmacology*; D008314:Malonates / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology
D004140:Dinitrophenols; D007656:Ketoglutaric Acids; D008298:Maleates; D008314:Malonates; D009840:Oligomycins; D010710:Phosphates; D013386:Succinates; D012402:Rotenone; D000968:Antimycin A; D008274:Magnesium; D001151:Arsenic