Lodato R F, Smith R J, Valle D, Phang J M, Aoki T T
Metabolism. 1981 Sep;30(9):908-13. doi: 10.1016/0026-0495(81)90070-6.
Mammalian cells have the capacity for proline biosynthesis from ornithine or glutamic acid. Using a radioisotopic assay, we have studied the regulation by ornithine of delta 1-pyrroline-5-carboxylate synthase, the enzyme that catalyzes the first step of proline biosynthesis from glutamic acid. In homogenates from Chinese hamster ovary cells, ornithine was found to be a potent inhibitor of pyrroline-5-carboxylate synthase activity(50% inhibition at 0.37 mM). The effect was reversible and did not occur with amino acids other than ornithine. Preliminary findings suggest that the inhibition does not result from altered requirements for the cofactors NADPH and ATP. Significant inhibition was observed in four different Chinese hamster cell lines. Ornithine was also shown to inhibit the conversion of 3H-glutamic acid to 3H-proline in intact human skin fibroblasts. Cells from patients with a rare ocular disease, gyrate atrophy of the choroid and retina, were used for these studies since they lack interfering ornithine aminotransferase activity. We conclude that ornithine may be a physiologic regulator of the rate of proline formation from glutamic acid. This information allows us to construct an hypothetical model for the overall regulation of proline biosynthesis and also to suggest a pathophysiologic mechanism for the disease gyrate atrophy.
哺乳动物细胞具有从鸟氨酸或谷氨酸合成脯氨酸的能力。我们使用放射性同位素分析法，研究了鸟氨酸对δ1-吡咯啉-5-羧酸合成酶的调节作用，该酶催化从谷氨酸合成脯氨酸的第一步反应。在中国仓鼠卵巢细胞的匀浆中，发现鸟氨酸是脯氨酸-5-羧酸合成酶活性的有效抑制剂（在0.37 mM时抑制率达50%）。这种作用是可逆的，且除鸟氨酸外的其他氨基酸不会产生这种作用。初步研究结果表明，这种抑制作用并非由对辅因子NADPH和ATP需求的改变所致。在四种不同的中国仓鼠细胞系中均观察到了显著的抑制作用。鸟氨酸还被证明能抑制完整人皮肤成纤维细胞中3H-谷氨酸向3H-脯氨酸的转化。由于患有罕见眼部疾病——脉络膜和视网膜回旋状萎缩症的患者的细胞缺乏干扰性的鸟氨酸转氨酶活性，因此使用这些患者的细胞进行了这些研究。我们得出结论，鸟氨酸可能是谷氨酸合成脯氨酸速率的生理调节因子。这一信息使我们能够构建一个脯氨酸生物合成整体调节的假设模型，并为回旋状萎缩症提出一种病理生理机制。
