Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria.
1. The specific activities of 4-aminobutyrate aminotransferase (EC 2.6.1.19) and succinate semialdehyde dehydrogenase (EC 1.2.1.16) were significantly higher in brain mitochondria of non-synaptic origin (fraction M) than those derived from the lysis of synaptosomes (fraction SM2). 2. The metabolisms of 4-aminobutyrate in both 'free' (non-synaptic, fraction M) and 'synaptic' (fraction SM2) rat brain mitochondria was studied under various conditions. 3. It is proposed that 4-aminobutyrate enters both types of brain mitochondria by a non-carrier-mediated process. 4. The rate of 4-aminobutyrate metabolism was in all cases higher in the 'free' (fraction M) brain mitochondria than in the synaptic (fraction SM2) mitochondria, paralleling the differences in the specific activities of the 4-aminobutyrate-shunt enzymes. 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase. 6. The redox state of the intramitochondrial NAD pool is also important in the control of 4-aminobutyrate metabolism; NADH exhibits competitive inhibition of 4-aminobutyrate metabolism by both mitochondrial populations with an apparent Ki of 102 muM. 7. Increased potassium concentrations stimulate 4-aminobutyrate metabolsim in the synaptic mitochondria but not in 'free' brain mitochondria. This is discussed with respect to the putative transmitter role of 4-aminobutyrate.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000096:biosynthesis; D001692:Biological Transport; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D005971:Glutamates / Q000096:biosynthesis; D007656:Ketoglutaric Acids / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D005971:Glutamates; D007656:Ketoglutaric Acids; D012402:Rotenone; D009243:NAD; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; D000612:4-Aminobutyrate Transaminase; D011188:Potassium