Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine O-sulphate in vitro and in vivo

Abstract

1. Partially purified preparations of rat brain 4-aminobutyrate aminotransferase were inhibited in a time-dependent manner by ethanolamine O-sulphate. The inhibition was not reversed by dialysis. 2. The inhibitor formed an initial reversible complex with the enzyme (K_i=4.4×10⁻⁴m) and the rate of inactivation followed pseudo-first-order kinetics (k=7.15×10⁻⁴s⁻¹). The inclusion of 4-aminobutyrate markedly slowed the rate of inactivation. 3. Ethanolamine O-sulphate did not inhibit glutamate decarboxylase, alanine aminotransferase or aspartate aminotransferase. 4. Intracisternal injection of ethanolamine O-sulphate into rats led to rapid inactivation of 4-aminobutyrate aminotransferase in vivo.