Mode of Inhibition of Ornithine Aminotransferase by L-Canaline
1978 年 83 巻 1 号 p. 201-206
詳細
1978 年 83 巻 1 号 p. 201-206
The mechanism of inhibition of ornithine aminotransferase [EC 2. 6. 1. 13] by L-canaline (α-amino-γ-amino-oxybutyric acid) was investigated. Spectral changes of pyridoxal 5'-phosphate in ornithine aminotransferase on addition of L-canaline showed that L-canaline formed an oxime-type compound with pyridoxal 5'-phosphate that had the same spectra as the compound formed on addition of hydroxylamine to the holoenzyme. Kinetic studies indicated that hydroxylamine was a reversible noncompetitive inhibitor, whereas L-canaline was an irreversible inhibitor of ornithine aminotransferase. Other analogs, such as δ-aminovaleric acid and α-N-acetyl-L-ornithine, also reacted with the pyridoxal 5'-phosphate of the enzyme, but these compounds were competitive inhibitors with respect to L-ornithine. L-Canaline and hydroxylamine also reacted with pyridoxal 5'-phosphate in pig heart aspartate aminotransferase [EC 2.6.1.1] to produce an oxime, but both of them were reversible and noncompetitive inhibitors of the enzyme. The K1 value of hydroxylamine for ornithine aminotransferase was 4.3×10-7M and those of L-canaline and hydroxylamine for aspartate aminotransferase were 1.7×10-4M and 2.2×10-5 M, respectively.
