Tomoda H, Igarashi K, Omura S
Kitasato Institute, Kitasato University, Tokyo, Japan.
Biochim Biophys Acta. 1987 Oct 17;921(3):595-8.
Triacsin A, 1-hydroxy-3-(E,E-2',4'-undecadienylidine) triazene and triacsin C, 1-hydroxy-3-(E,E,E-2',4',7'-undecatrienylidine) triazene are potent inhibitors of acyl-CoA synthetase (EC 6.2.1.3). The concentrations of triacsin A required for 50% inhibition of acyl-CoA synthetase from Pseudomonas aeruginosa and from rat liver are 17 and 18 microM, and those of triacsin C are 3.6 and 8.7 microM, respectively. Kinetic analysis indicates that inhibition of triacsin A is non-competitive with respect to the two substrates ATP and coenzyme A, but is competitive with respect to long-chain fatty acids. The apparent Ki value is 8.97 microM when oleic acid is used as substrate. Acid hydrolysis of triacsins results in corresponding polyenic aldehydes with no activity. This suggests that the N-hydroxytriazene moiety is essential for inhibitory activity against acyl-CoA synthetase.
曲菌素A，即1-羟基-3-（E，E-2'，4'-十一碳二烯叉基）三氮烯，以及曲菌素C，即1-羟基-3-（E，E，E-2'，4'，7'-十一碳三烯叉基）三氮烯，都是酰基辅酶A合成酶（EC 6.2.1.3）的强效抑制剂。对铜绿假单胞菌和大鼠肝脏中的酰基辅酶A合成酶产生50%抑制作用所需的曲菌素A浓度分别为17和18微摩尔，而曲菌素C的浓度分别为3.6和8.7微摩尔。动力学分析表明，曲菌素A对两种底物ATP和辅酶A的抑制作用是非竞争性的，但对长链脂肪酸的抑制作用是竞争性的。以油酸为底物时，表观Ki值为8.97微摩尔。曲菌素经酸水解会生成相应的多烯醛，且无活性。这表明N-羟基三氮烯部分对酰基辅酶A合成酶的抑制活性至关重要。
