Lodato R F, Smith R J, Valle D L, Crane K
J Cell Physiol. 1984 Apr;119(1):137-43. doi: 10.1002/jcp.1041190122.
Two mutant Chinese hamster lung fibroblast lines have been isolated that are resistant to the toxic proline analog L-azetidine-2-carboxylic acid. The line designated AZCA-1 has 30-fold elevated activity of pyrroline-5-carboxylate synthase and a large increase in the rate of proline production and release compared to controls. Pyrroline-5-carboxylate synthase activity is not elevated in the resistant line designated AZCA-4, but the enzyme is less sensitive to inhibition by ornithine and proline than control enzyme. Intracellular proline is elevated in AZCA-4 cells, with no change in the rate of release of proline synthesized from glutamate. Resistance to azetidine carboxylic acid in both mutant lines is attributed to the expanded intracellular proline pool that results from alterations in pyrroline-5-carboxylate synthase. These results indicate that intracellular proline levels are determined at least in part by the regulated activity of pyrroline-5-carboxylate synthase.
已分离出两种对有毒脯氨酸类似物L-氮杂环丁烷-2-羧酸具有抗性的中国仓鼠肺成纤维细胞突变株系。命名为AZCA-1的株系中，吡咯啉-5-羧酸合酶的活性比对照高30倍，脯氨酸的产生和释放速率也大幅增加。在命名为AZCA-4的抗性株系中，吡咯啉-5-羧酸合酶的活性并未升高，但该酶对鸟氨酸和脯氨酸抑制作用的敏感性低于对照酶。AZCA-4细胞内的脯氨酸含量升高，而由谷氨酸合成的脯氨酸的释放速率没有变化。两个突变株系对氮杂环丁烷羧酸的抗性归因于吡咯啉-5-羧酸合酶改变导致的细胞内脯氨酸池扩大。这些结果表明，细胞内脯氨酸水平至少部分由吡咯啉-5-羧酸合酶的调节活性决定。
