Inhibition of the oxidation of glutamate and isocitrate in liver mitochondria at a specific NADP+-reducing site.
The cation-complexing carboxylic-acid antibiotic X-537A, at concentrations far below that required for ionophorous activity, selectively inhibits the oxidation of glutamate and isocitrate by liver mitochondria in steady-state 3. The site of inhibition has been localized specifically at the reduction of NADP(+). Glutamate and isocitrate dehydrogenases, the oxidation of NAD(+)-dependent substrates, pyridine nucleotide transhydrogenations, and the respiratory chain between NADH (or NADPH) and O(2) are unaffected by the antibiotic X-537A. Kinetic evidence, i.e., competition between chlorotetracycline (a fluorescence probe for membrane-bound bivalent cation) and X-537A, indicates that the NADP(+)-reducing, antibiotic-sensitive site is most probably associated with the inner mitochondrial membrane.
D000244:Adenosine Diphosphate; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001565:Benzoates / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002264:Carboxylic Acids / Q000378:metabolism / Q000494:pharmacology*; D002751:Chlortetracycline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport; D005971:Glutamates / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism; D066298:In Vitro Techniques; D007523:Isocitrates / Q000378:metabolism*; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013386:Succinates / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001565:Benzoates; D002264:Carboxylic Acids; D005971:Glutamates; D006885:Hydroxybutyrates; D007523:Isocitrates; D008293:Malates; D011773:Pyruvates; D013386:Succinates; D009249:NADP; D000244:Adenosine Diphosphate; D002751:Chlortetracycline