1. The specific activities of 4-aminobutyrate aminotransferase (EC 188.8.131.52) and succinate semialdehyde dehydrogenase (EC 184.108.40.206) 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.
Research Article| November 15 1976
Studies on the control of 4-aminobutyrate metabolism in ‘synaptosomal’ and free rat brain mitochondria
J M Walsh;
Biochem J (1976) 160 (2): 147–157.
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J M Walsh, J B Clark; Studies on the control of 4-aminobutyrate metabolism in ‘synaptosomal’ and free rat brain mitochondria. Biochem J 15 November 1976; 160 (2): 147–157. doi: https://doi.org/10.1042/bj1600147
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