Fig. 2: Ferroptosis and amino acid metabolism.
From: Metabolism-regulated ferroptosis in cancer progression and therapy
Glutamate, cysteine and glycine are the composition of GSH, which is the negative regulator of ferroptosis. Intracellular glutamate is generated from glutamine. Cystine can be transported into cancer cells by system Xc− and is reduced to cysteine. High levels of extracellular glutamate inhibit the activity of system Xc−. Besides, cysteine can be generated from serine, which also participate in the synthesis of glycine. The enzymes in amino acid metabolism suppress ferroptosis via regulating SLC7A11, labile iron and GPX4. Glu glutamate, Gln glutamine, SLC38A1 solute carrier family 38 member 1, SLC1A5 solute carrier family 1 member 5, SLC7A11 solute carrier family 7 member 11, SLC3A2 solute carrier family 3 member 2, AAs amino acids, ADCY10 adenylyl cyclase 10, PKA protein kinase A, GFPT1 glutamine-fructose-6-phosphate transaminase, YAP yes-associated protein, GCLC glutamate-cysteine ligase catalytic subunit, GCL glutamate-cysteine ligase, GSS glutathione synthetase, GSH reduced glutathione, GPX4 glutathione peroxidase 4, 3PG 3-phosphoglycerate, PHGDH phosphoglycerate dehydrogenase, CBS cystathionine beta-synthase, CSE cystathionine gamma-lyase, SAM S-adenosylmethionine, Met methionine, ACSL3 long-chain acyl-CoA synthetase 3 (Created with BioRender.com).
