Shuttle between arginine and lysine: influence on cancer immunonutrition

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.