Inhibitory Actions of Mycotoxins on Brain $\gamma$-Aminobutyrate Transaminase

$\gamma$-Aminobutyrate Transaminase에 대한 Mycotoxin의 저해작용

GABA transminase (4-aminobutyrate aminotransferase), which catalyzes the breakdown of the major inhibitory neurotransmitter, GABA, in mammalian brain, was inactivated by preincubation with the mycotoxin patulin. The time course of the reaction was significantly affected by the substrate .alpha.-ketoglutarate, which aforded complete protection against the loss of catalytic activity. The recovery from the inhibition of patulin by the addition of dithiothreitol (DTT) supports that patulin reacts with the sulfhydryl residue in the catalytic domain of the enzyme. The reconstitution of the reduced enzyme and apoenzyme with pyridoxal-5-P(PLP) was inhibited by another mycotoxin, penicilic acid. This mycotoxin may interact with lysyl residue of the enzyme. Therefore, it is postulated that the critical sulfhydryl and lysyl residues in the catalytic domain of the enzyme react with mycotoxin patulin and penicillic acid, respectively.