Department of Microbiology, JSS-Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India.
Department of Biotechnology and Bioinformatics, JSS-Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India.
Amino Acids. 2023 Nov;55(11):1461-1473. doi: 10.1007/s00726-023-03327-9. Epub 2023 Sep 20.
Amino acids which are essential nutrients for all cell types' survival are also recognised to serve as opportunistic/alternative fuels in cancers auxotrophic for specific amino acids. Accordingly, restriction of amino acids has been utilised as a therapeutic strategy in these cancers. Contrastingly, amino acid deficiencies in cancer are found to greatly impair immune functions, increasing mortality and morbidity rates. Dietary and supplemental amino acids in such conditions have revealed their importance as 'immunonutrients' by modulating cellular homeostasis processes and halting malignant progression. L-arginine specifically has attracted interest as an immunonutrient by acting as a nodal regulator of immune responses linked to carcinogenesis processes through its versatile signalling molecule, nitric oxide (NO). The quantum of NO generated directly influences the cytotoxic and cytostatic processes of cell cycle arrest, apoptosis, and senescence. However, L-lysine, a CAT transporter competitor for arginine effectively limits arginine input at high L-lysine concentrations by limiting arginine-mediated effects. The phenomenon of arginine-lysine antagonism can, therefore, be hypothesised to influence the immunonutritional effects exerted by arginine. The review highlights aspects of lysine's interference with arginine-mediated NO generation and its consequences on immunonutritional and anti-cancer effects, and discusses possible alternatives to manage the condition. However, further research that considers monitoring lysine levels in arginine immunonutritional therapy is essential to conclude the hypothesis.
氨基酸是所有细胞类型生存所必需的营养物质，也被认为是特定氨基酸营养缺陷型癌症的机会性/替代燃料。因此，限制氨基酸已被用作这些癌症的治疗策略。相比之下，癌症中氨基酸的缺乏被发现极大地损害了免疫功能，增加了死亡率和发病率。在这种情况下，饮食和补充氨基酸已被证明作为“免疫营养素”具有重要意义，因为它们通过调节细胞内稳态过程和阻止恶性进展来发挥作用。精氨酸特别作为一种免疫营养素引起了人们的兴趣，它通过其多功能信号分子一氧化氮 (NO) 作为与致癌过程相关的免疫反应的节点调节剂发挥作用。产生的 NO 量直接影响细胞周期停滞、细胞凋亡和衰老的细胞毒性和细胞抑制过程。然而，精氨酸的 CAT 转运体竞争物赖氨酸在高赖氨酸浓度下通过限制精氨酸介导的作用有效地限制了精氨酸的输入。因此，可以假设精氨酸-赖氨酸拮抗现象会影响精氨酸发挥的免疫营养作用。该综述强调了赖氨酸干扰精氨酸介导的 NO 生成及其对免疫营养和抗癌作用的后果的方面，并讨论了管理这种情况的可能替代方法。然而，考虑在精氨酸免疫营养治疗中监测赖氨酸水平的进一步研究对于得出结论是必要的。
