Human brain GABA transaminase tissue distribution and molecular expression

Human brain γ-aminobutyrate transaminase is differentially expressed in a tissue-specific manner. mRNA master dot-blot analysis for 50 different human tissues, including different brain regions and fetal tissues, provided a complete map of the tissue distribution. Genomic Southern analysis revealed that the γ-aminobutyrate transaminase gene is a single copy, at least 15 kb in size. In addition, human brain γ-aminobutyrate transaminase cDNA was expressed in Escherichia coli using a pGEX expression vector system. Catalytically active γ-aminobutyrate transaminase was expressed in large quantities and the purified recombinant enzyme had kinetic parameters that were indistinguishable from those isolated from other mammalian brains. The human enzyme was inactivated by a well-known anfiepileptic drug vigabatrin. Values of K(i) and k(inact) were 1 mM and 0.35 min^-1, respectively. Results from inactivation kinetics suggested that human γ-aminobutyrate transaminase is more sensitive to the vigabatrin drug than the enzyme isolated from bovine brain.