Phthalonic acid, an inhibitor of alpha-oxoglutarate transport in mitochondria.
Phthalonic acid is a powerful inhibitor of alpha-oxoglutarate transport in mitochondria. This conclusion is based on the following observations: 1. Phthalonic acid inhibits the oxidation of alpha-oxoglutarate but has no effect on the oxidation of glutamate or cis-aconitate. 2. With arsenite present, phthalonic acid inhibits the oxidation of glutamate plus malate and of cis-aconitate plus malate. Under these conditions alpha-oxoglutarate accumulates inside the mitochondria. With glutamate plus malate as substrates the inhibition is competitive with malate with a Ki value of 20 muM. 3. Phthalonic acid inhibits the oxidation of intramitochondrial NAD(P)H by alpha-oxoglutarate plus ammonia. The inhibition is competitive with respect to alpha-oxoglutarate with a Ki of 30 muM. 4. Phthalonic acid inhibits the exchange between extramitochondrial alpha-oxoglutarate and intramitochondrial malate.
D000156:Aconitic Acid / Q000494:pharmacology; D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000378:metabolism*; D007700:Kinetics; D008293:Malates / Q000494:pharmacology; D008314:Malonates / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010795:Phthalic Acids / Q000378:metabolism*; D051381:Rats
D005971:Glutamates; D007656:Ketoglutaric Acids; D008293:Malates; D008314:Malonates; D010795:Phthalic Acids; C012492:phthalonic acid; D000156:Aconitic Acid; D001151:Arsenic