This pathway represents biology relevant to glutathione, including biosynthesis, metabolism, redox cycle, uptake, glutathionylation and acivicin inhibition. Glutathione is an antioxidant that is synthesized in eukaryotes from L-cysteine, L-glutamic acid, and glycine in a two-step process involving gamma-glutamylcysteine synthetase and glutathione synthetase. Glutathione prevents cellular damage by acting as an electron donor to neutralize reactive oxygen species. Reactive glutathione is produced, which then reacts with another reactive glutathione molecule to produce glutathione disulfide, GSSG. It was based partly on [[Pathway:WP164 |WP164]] and [[Pathway:WP1770|WP1770]], with information added from literature. This pathway was created as a part of [https://www.nature.com/articles/s41590-020-0654-0 Mendiola et cl], pictured in fig 5. d6d CD44 interacts with and stabilizes XCT b7f System Xc- is an antiporter that transports Cystine in and glutamate out. https://en.wikipedia.org/wiki/SLC7A11 (5-L-Glutamyl)-L-amino acid f3f f20 Nrf2 controls expression of Gpx2 bcc c3e c3e Nrf2 controls the expression of Gclc and Gclm bcc c3e TF targeting of Idh1 per AW analysis Predicted interaction (GenMANIA) ab8 System Xc- is an antiporter that transports Cystine in and glutamate out. https://en.wikipedia.org/wiki/SLC7A11 Nrf2 controls expression of PGd, Idh1, G6pd, Me1 bcc b53 b53 bcc e60 b53 edd b9a b9a Nrf2 controls expression of PGd, Idh1, G6pd, Me1 bcc 15988009 PubMed Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Mol Cell Biol 2005 Yang H Magilnick N Lee C Kalmaz D Ou X Chan JY Lu SC glutathione metabolic pathway PW:0000134 Pathway Ontology 22500213 PubMed Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acids 2012 Lushchak VI 32284594 PubMed Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation 2020 Andrew S. Mendiola Jae Kyu Ryu Sophia Bardehle Anke Meyer-Franke Kenny Kean-Hooi Ang Chris Wilson Kim M. Baeten Kristina Hanspers Mario Merlini Sean Thomas Mark A. Petersen Alexander Williams Reuben Thomas Victoria A. Rafalski Rosa Meza-Acevedo Reshmi Tognatta Zhaoqi Yan Samuel J. Pfaff Michael R. Machado Catherine Bedard Pamela E. Rios Coronado Xiqian Jiang Jin Wang Michael A. Pleiss Ari J. Green Scott S. Zamvil Alexander R. Pico Benoit G. Bruneau Michelle R. Arkin Katerina Akassoglou 18786560 PubMed Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Mol Aspects Med 2009 Ballatori N Krance SM Marchan R Hammond CL glutathione biosynthetic pathway PW:0001277 Pathway Ontology glutathione antioxidant pathway PW:0002623 Pathway Ontology 23770340 PubMed Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo. Free Radic Biol Med 2013 Timme-Laragy AR Goldstone JV Imhoff BR Stegeman JJ Hahn ME Hansen JM 27579494 PubMed Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis. J Neurochem 2016 Morales Pantoja IE Hu CL Perrone-Bizzozero NI Zheng J Bizzozero OA 24647116 PubMed The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 2014 Hayes JD Dinkova-Kostova AT 21037289 PubMed Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J Biol Chem 2010 Yan Z Garg SK Banerjee R 24287781 PubMed Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 2013 Gorrini C Harris IS Mak TW 20215646 PubMed Stress-activated cap'n'collar transcription factors in aging and human disease. Sci Signal 2010 Sykiotis GP Bohmann D 18818725 PubMed A genomewide functional network for the laboratory mouse. PLoS Comput Biol 2008 Guan Y Myers CL Lu R Lemischka IR Bult CJ Troyanskaya OG classic metabolic pathway PW:0000002 Pathway Ontology