Fig. 4.

Amino acid metabolism regulates tumor angiogenesis. The metabolism of amino acids can impact not only the function of endothelial cells but also the formation and function of blood vessels. Glutamine is catalyzed by GLS to form glutamate, which can be converted to aspartate to promote endothelial cell germination. Glutamate can also be converted to P5C and proline, further facilitating ECM remodeling. Following VEGF signaling stimulation, endothelial cells exhibit increased glycine uptake, which can enhance endothelial cell migration. Glycine is also involved in GSH synthesis, inhibiting vascular tone, blood pressure, and oxidative stress mediated by NO. Arginine, through the synthesis of proline, polyamines, and NO, plays a regulatory role in angiogenesis. The serine synthesis pathway dependent on PHGDH can promote antihypertensive effects, regulate oxidative stress, and resist endothelial cell apoptosis. Additionally, tryptophan metabolism in MDSCs generates kynurenine via IDO-1, regulating the balance between IFNγ and IL6. While IL6 promotes angiogenesis, IFNγ exerts the opposite effect. GSH glutathione, GLS glutaminase, ECM extracellular matrix, VEGF vascular Endothelial Growth Factor, PHGDH phosphoglycerate dehydrogenase. Image created with BioRender.com