Mode of inhibition of ornithine aminotransferase by L-canaline.
The mechanism of inhibition of ornithine aminotransferase [EC 2.6.1.13] by L-canaline (alpha-amino-gamma-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 delta-aminovaleric acid and alpha-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 Ki value of hydroxylamine for ornithine aminotransferase was 4.3 X 10(-7) M and those of L-canaline and hydroxylamine for aspartate aminotransferase were 1.7 X 10(-4) M and 2.2 X 10(-5) M, respectively.
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000613:Aminobutyrates / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001665:Binding Sites; D006898:Hydroxylamines / Q000494:pharmacology; D007700:Kinetics; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors*; D011732:Pyridoxal Phosphate; D000637:Transaminases / Q000037:antagonists & inhibitors*; D014631:Valerates / Q000494:pharmacology
D000596:Amino Acids; D021542:Amino Acids, Neutral; D000613:Aminobutyrates; D006898:Hydroxylamines; D014631:Valerates; C001926:canaline; D011732:Pyridoxal Phosphate; C013809:5-aminovaleric acid; D009952:Ornithine; D000637:Transaminases; D001219:Aspartate Aminotransferases; D009953:Ornithine-Oxo-Acid Transaminase