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It is secreted by I-cells in the duodenal and small bowel mucosa in response to protein and fat, with its main effects on the liver, gallbladder, pancreas and, interestingly, central nervous system (CNS)

Probably some combination applies to differing degrees for different metalloenzymes and cofactors

doi: 10.3389/fncel.2025.1669272 Received 19 July 2025 Revised 10 December 2025 Accepted 12 December 2025 Published 17 February 2026 Volume 19 - 2025 Edited by Luca Raiteri, University of Genoa, Italy Reviewed by Cataldo Arcuri, University of Perugia, Italy Updates Copyright 2026 Uemura, Hiro, Attachaipanich, Du, Yusof, Kinoshita, Hikosaka and Ohtsuki

Perluigi M, Tramutola A, Pagnotta S et al (2020) The BACH1/Nrf2 axis in brain in down syndrome and transition to Alzheimer disease-like neuropathology and dementia

Mechanistically, ROS stabilizes HIF-1 and upregulates VEGF by activating several pathways

Glutathione Transferase A1-1: Catalytic Importance of Arginine 15