The inhibition by substrate analogues of gamma-aminobutyrate aminotransferase from mitochondria of different subcellular fractions of rat brain.
Cytoplasmic-mitochondria-enriched and synaptosome-enriched subcellular fractions were prepared from rat brain to study certain kinetic properties of gamma-aminobutyrate: alpha-oxoglutarate aminotransferase (GABA-T) (EC 2.6.1.19) from each of the sources. From this study two differences emerged. Firstly, the cytoplasmic enzyme exhibited an eightfold greater affinity for gamma-aminobutyric acid (GABA) than did the synaptosomal GABA-T; the Km being 6.5 mM and 53 mM, respectively. Secondly, synaptosomal GABA-T is comparatively more susceptible to inhibition by the substrate analogues 2,4-diaminobutyric acid (DABA) and aminooxyacetic acid (AOAA) than is the enzyme from the cytoplasmic mitochondrial fraction. In each case the inhibition was of a competitive nature with respect to GABA. The Ki for the DABA was 13 mM for the cytoplasmic-derived enzyme and 8mM for the synaptosomal enzyme. With AOAA the Ki was 0.1 muM and 0.06 muM for the synaptosomal and cytoplasmic mitochondrial enzyme, respectively. These results provide further evidence that GABA-T from cytoplasmic mitochondria is different in several respects from the enzyme found in synaptosomes.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008928:Mitochondria / Q000201:enzymology*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology; D013574:Synaptosomes / Q000201:enzymology; D000637:Transaminases / Q000037:antagonists & inhibitors*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives
D005680:gamma-Aminobutyric Acid; D000637:Transaminases; D000612:4-Aminobutyrate Transaminase