Department of Biochemistry and Molecular Biology, Biocenter, D-97074 Wuerzburg, Germany.
Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wuerzburg, D-97070 Wuerzburg, Germany.
Int J Mol Sci. 2021 Oct 27;22(21):11630. doi: 10.3390/ijms222111630.
Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.
蛋氨酸限制（MetR）是一种在细胞和生物体中有效限制氨基酸（AR）的方法，它诱导类似于热量限制（CR）的低能量代谢（LEM）。由于饮食中去除单一氨基酸非常困难，因此将 MetR 作为癌症或其他疾病的治疗方法并不简单。然而，胱氨酸的体内周转率通常高于通过食物摄入的速度。出于这个原因，每个细胞都可以从蛋氨酸酶促合成胱氨酸，这使得可以使用特定的酶抑制剂。在这项工作中，我们分析了胱氨酸限制（CysR）在 L929 鼠细胞系中的潜力。这项研究使用质谱法（LC/MS）分析代谢指纹图谱。将这些图谱与在 MetR 下创建的早期工作中的图谱进行比较。该研究通过使用 D-氨基酸类似物和细胞内胱氨酸合成抑制剂的增殖研究进行了补充。CysR 显示出与 MetR 相当的增殖抑制潜力。然而，代谢足迹差异显著，表明 CysR 在代谢水平上不会诱导经典的 LEM。尽管如此，CysR 作为一般和肿瘤代谢水平上决定性干预的替代方法具有很大的潜力。
