Schirlin D, Baltzer S, Heydt J G, Jung M J
Merrell Dow Research Institute, Strasbourg Center, France.
J Enzyme Inhib. 1987;1(4):243-58. doi: 10.3109/14756368709020122.
beta-Difluoromethyl-beta-alanine (3-amino-4,4-difluorobutanoic acid) is a potent in vitro and in vivo inhibitor of GABA-T. The rate of inhibition of GABA-T is concentration- and time-dependent. The inactivation is active-site directed. No reactive species escapes from the active site before reacting with the enzyme. The inhibition is irreversible and stereospecific. The use of beta-2H-beta-difluoromethyl-beta-alanine results in a marked primary isotope effect in vitro and in vivo. The use of differently substituted dihalogeno derivatives of beta-alanine suggests that the rate of inhibition is dependent on the nature and position of the leaving group. The mechanism of inhibition is discussed on the basis of spectral changes.
β-二氟甲基-β-丙氨酸（3-氨基-4,4-二氟丁酸）是一种在体外和体内均有效的γ-氨基丁酸转氨酶（GABA-T）抑制剂。GABA-T的抑制速率呈浓度和时间依赖性。失活作用是活性位点导向的。在与酶反应之前，没有反应性物种从活性位点逸出。这种抑制是不可逆的且具有立体特异性。使用β-2H-β-二氟甲基-β-丙氨酸在体外和体内均产生显著的一级同位素效应。使用β-丙氨酸的不同取代二卤代衍生物表明，抑制速率取决于离去基团的性质和位置。基于光谱变化对抑制机制进行了讨论。
