Stieglitz B, Calvo J M
J Bacteriol. 1971 Oct;108(1):95-104. doi: 10.1128/jb.108.1.95-104.1971.
dl-4-Azaleucine (5 x 3(-3)m) added to exponentially growing cells of Salmonella typhimurium resulted in an abrupt cessation of growth lasting 4 to 8 hr followed by a resumption of division. The transitory nature of inhibition was not due to the instability or modification of the analogue or to a derepression of leucine-forming enzymes. Of many compounds tested, leucine served most efficiently to reverse 4-azaleucine-induced inhibition. Inhibition of growth can be explained by the fact that 4-azaleucine inhibits alpha-isopropylmalate synthase, the first enzyme unique to leucine biosynthesis. The analogue was a poor inhibitor of both the transamination of alpha-ketoisocaproate to leucine and the charging of leucine to transfer ribonucleic acid. With a leucine auxotroph starved for leucine, the analogue was incorporated into protein specifically in place of leucine. Such incorporation was accompanied by the death of almost all of the cells.
将dl-4-氮杂亮氨酸（5×10⁻³m）添加到鼠伤寒沙门氏菌指数生长期的细胞中，会导致生长突然停止4至8小时，随后恢复分裂。抑制的短暂性并非由于类似物的不稳定性或修饰，也不是由于亮氨酸形成酶的去阻遏。在测试的许多化合物中，亮氨酸最有效地逆转了4-氮杂亮氨酸诱导的抑制。生长抑制可以通过以下事实来解释：4-氮杂亮氨酸抑制α-异丙基苹果酸合酶，这是亮氨酸生物合成中第一个独特的酶。该类似物对α-酮异己酸向亮氨酸的转氨作用以及亮氨酸与转移核糖核酸的负载作用都是较差的抑制剂。对于缺乏亮氨酸的亮氨酸营养缺陷型菌株，该类似物会特异性地取代亮氨酸掺入蛋白质中。这种掺入几乎伴随着所有细胞的死亡。
