title: The inhibition of mitochondrial dicarboxylate transport by inorganic phosphate, some phosphate esters and some phosphonate compounds.
abstract: 1. P(i) competitively inhibited succinate oxidation by intact uncoupled mitochondria in the presence of sufficient N-ethylmaleimide to block the phosphate carrier, with a K(i) of 2.5mm. 2. Of a large number of phosphate esters and phosphonate compounds, phenyl phosphate and phenylphosphonate were found to inhibit competitively uncoupled succinate oxidation by intact but not broken mitochondria. By comparison, benzoate was a relatively weak competitive inhibitor of succinate oxidation by intact mitochondria but a relatively potent inhibitor of succinate dehydrogenase. 3. Phenyl phosphate and phenylphosphonate were non-penetrant, and inhibited P(i)-dependent swelling of mitochondria suspended in isosmolar ammonium malate in a manner non-competitive with P(i). The inhibitors did not affect mitochondrial swelling when tested with P(i) alone. 4. It is concluded that: (i) phenyl phosphate and phenylphosphonate behaved as non-penetrant analogues of P(i), since their inhibitory properties were in strict contrast with those of benzoate; (ii) phenyl phosphate and phenylphosphonate interacted with the dicarboxylate carrier but not with the phosphate carrier; (iii) P(i) was effective as a competitive inhibitor of succinate oxidation because of its being either an alternative substrate for the dicarboxylate carrier or competitive with succinate for the intramitochondrial cations as proposed by Harris & Manger (1968).
mesh_terms: D000249:Adenosine Monophosphate / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001692:Biological Transport; D004952:Esters / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005636:Fructosephosphates / Q000494:pharmacology; D005958:Glucosephosphates / Q000494:pharmacology; D005994:Glycerophosphates / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009596:Nitrophenols / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*; D010756:Phosphoric Acids / Q000494:pharmacology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D013386:Succinates / Q000378:metabolism*
chemical_list: D001565:Benzoates; D004952:Esters; D005636:Fructosephosphates; D005958:Glucosephosphates; D005994:Glycerophosphates; D009596:Nitrophenols; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010710:Phosphates; D010756:Phosphoric Acids; D013386:Succinates; D000249:Adenosine Monophosphate; D013385:Succinate Dehydrogenase; D005033:Ethylmaleimide