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肿瘤的反应是否取决于某些氨基酸的饮食摄入或必需氨基酸与非必需氨基酸之间的比例?闪光的未必都是金子。

Is the Response of Tumours Dependent on the Dietary Input of Some Amino Acids or Ratios among Essential and Non-Essential Amino Acids? All That Glitters Is Not Gold.

机构信息

Determinants of Metabolism Research Laboratory, 20137 Milan, Italy.

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

出版信息

Int J Mol Sci. 2018 Nov 17;19(11):3631. doi: 10.3390/ijms19113631.

Abstract

Energy production is the main task of the cancer cell metabolism because the costs of duplicating are enormous. Although energy is derived in cells by dismantling the carbon-to-carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as being dependent on glycolysis. Since the end of the last century, the awareness of the dependence of cancer metabolism on amino acids not only for protein synthesis but also to match energy needs has grown. The roles of specific amino acids such as glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, epidemiological evidence has revealed that some amino acids used as a supplement for therapeutic reasons, particularly the branched-chain ones, may reduce the incidence of liver cancer and a specific molecular mechanism has been proposed as functional to their protective action. By contrast and puzzling clinicians, the metabolomic signature of some pathologies connected to an increased risk of cancer, such as prolonged hyperinsulinemia in insulin-resistant patients, is identified by elevated plasma levels of the same branched-chain amino acids. Most recently, certain formulations of amino acids, deeply different from the amino acid compositions normally present in foods, have shown the power to master cancer cells epigenetically, slowing growth or driving cancer cells to apoptotic death, while being both beneficial for normal cell function and the animal's health and lifespan. In this review, we will analyze and try to disentangle some of the many knots dealing with the complexities of amino acid biology and links to cancer metabolism.

摘要

能量产生是癌细胞代谢的主要任务,因为复制的成本是巨大的。尽管细胞通过拆解任何大量营养素的碳-碳键来产生能量,但癌症对能量的营养需求主要被研究为依赖糖酵解。自上个世纪末以来,人们越来越意识到癌症代谢不仅依赖于氨基酸用于蛋白质合成,还依赖于满足能量需求。已经在不同的实验条件下探索了特定氨基酸(如谷氨酰胺、甘氨酸和丝氨酸)的作用,并进行了综述。此外,流行病学证据表明,一些用作治疗原因的氨基酸补充剂,特别是支链氨基酸,可能会降低肝癌的发病率,并提出了一种特定的分子机制作为其保护作用的功能。相比之下,一些与癌症风险增加相关的病理学的代谢组学特征令临床医生感到困惑,例如胰岛素抵抗患者的胰岛素长期升高,其特征是血浆中相同支链氨基酸水平升高。最近,某些氨基酸配方与正常食物中存在的氨基酸组成有很大的不同,已显示出能够在表观遗传学上控制癌细胞的能力,减缓生长或促使癌细胞凋亡,同时对正常细胞功能和动物的健康和寿命有益。在这篇综述中,我们将分析并试图解开一些与氨基酸生物学和与癌症代谢相关的复杂性有关的许多结。

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