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. Author manuscript; available in PMC: 2022 Sep 1.
Published in final edited form as: Cancer Discov. 2022 Mar 1;12(3):625–643. doi: 10.1158/2159-8290.CD-21-0922

Figure 3: Metabolic Rewiring by NRF2.

Figure 3:

Activation of NRF2 dramatically enhances generation of glutathione by increasing synthesis of glutathione from intracellular glutamate, cysteine, and glycine. Intracellular glutamate is derived from glutamine through GLS-1. Cystine is imported by the NRF2 target SLC7A11. Serine and glycine are synthesized via NRF2 dependent processes. NADPH is synthesized to support redox metabolism by the pentose phosphate pathway. GLS-1 and SLC7A11 function can be impaired by CB-839 and erastin respectively.

PHGD, phosphoglycerate dehydrogenase; PSAT1, phosphoserine aminotransferase; PSPH, phosphoserine phosphatase; SHMT, serine hydroxymethyltransferase; G6PD, glucose-6-phopshate dehydrogenase; PGLS, 6-phosphogluconolactonase; 6PGD, 6-phosphogluctonate dehydrogenase; TKT, transketolase; TAL, transaldolase; GPX4, glutathione peroxidase 4; GR, glutathione reductase; GLS1, glutaminase 1; GCLC, glutamate-cysteine ligase catalytic subunit; GCLM, glutamate-cysteine ligase modifier subunit; GSS, glutathione synthetase; TR, thioredoxin; NAD(P)H, nicotinic adenine dinucleotide (phosphate); PUFA, polyunsaturated fatty acid; THF, tetrahydrofolate