Differences in biochemical properties of gamma-aminobutyric acid aminotransferase from synaptosome-enriched and cytoplasmic mitochondria-enriched subcellular fractions of mouse brain.

Abstract

Using conventional subfractionation techniques on whole mouse brains, a minimum of two distinct sources of γ-aminobutyric acid (GABA) aminotransferase were detected. GABA-T from cytoplasmic mitochondria-enriched fraction ("cytoplasmic" GABA-T) exhibited a higher apparent affinity for GABA, and for two new analogues of GABA, than a similar enzyme originating from nerve ending-enriched fraction ("synaptosomal" GABA-T). The two analogues, β-chloro GABA and β-phenyl GABA, inhibited cytoplasmic aminotransferase in a competitive manner whereas the synaptosomal enzyme was inhibited noncompetitively. "Cytoplasmic" GABA-T demonstrated an optimal activity of pH 7 whereas GABA-T of nerve endings was most active at pH 8. Per milligram of protein, the GABA-T activity in synaptosomes was five times less than in cytoplasmic mitochondria.These findings may imply that GABA absorbed in neuronal perikarya and glia (cytoplasmic mitochondria) is rapidly destroyed. In contrast, the unfavorable pH optimum displayed by the synaptosomal GABA-T, its weaker affinity for GABA, and a lower GABA-T concentration per se would favor accumulation of GABA in the nerve terminals.