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The inhibitor of glutamine synthetase (GS) activity, l-methionine sulfoximine (MSO), has been shown to inhibit glutamine metabolism, induce a shift to M1-TAMs, and act as a potent antitumor immunity [123]

Chronic IFN-I stimulation perturbs lipid metabolism and redox balance in exhausted CD8 + T cells, leading to aberrant lipid accumulation and elevated lipid peroxidation, which exaggerates metabolic and functional exhaustion of T cells (46)

Low levels of ROS play essential roles in microbe killing and act as secondary messengers for intracellular signaling pathways involved in host immune responses

Additionally, in patients with folic acid deficiency, the plasma levels of methionine and betaine remain unchanged, and the DMG concentration increases, which suggests that betaine, acting as a methyl-group donor, is able to compensate for folic acid deficiencies and ensure the proper functioning of the one-carbon cycle [202,203]

Design and Structural Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with High In Vivo Potency and Oral Bioavailability