Figure 3.

Metabolism of glutamine, arginine, and tryptophan. Glutamine is available intracellularly for various anabolic pathways. Tumor cells exhibit glutamine dependence in ccRCC, upregulating SLC7A5 glutamine transporter protein and GLS enzymes to take up more glutamine and promote its conversion to glutamate, which maintains the redox state in vivo or to α-KG, an alternative substrate for the tricarboxylic acid cycle and synthesis of lipids. Tryptophan is degraded in the kynurenine pathway to produce immunosuppressive products, while in ccRCC, this process is upregulated by IOD, leading to the activation of the entire pathway. Arginine is synthesized from citrulline via ASS1, but AAS1 is not expressed or downregulated in ccRCC and cannot synthesize this amino acid and can only be taken up from the blood.