DMF is rapidly converted to bioactive monomethyl fumarate (MMF) in the gut and circulated to tissues. Inside cells, MMF is converted to fumarate, which binds kelch-like ECH-associated protein 1 (Keap1), resulting in dissociation of the Keap1-Nrf2 complex. Keap1 represses Nrf2 activity by targeting the complex for degradation by the ubiquitin proteosome. Once dissociated from Keap1, DJ-1 chaperones Nrf2 into the nucleus, where Nrf2 binds the antioxidant response element (ARE), initiating transcription of antioxidant genes superoxide dismutase 1 (SOD1), NAD(P)H dehydrogenase:quinone oxidoreductase (NQO1), catalase (CAT), and hemoxygenase-1 (HO-1). Meanwhile, Keap1 is sequestered by p62, which initiates autophagy and amplifies Nrf2-mediated ARE transcription. Fumarate also inhibits master inflammation regulator, nuclear factor κB (NF-κB), which suppresses nuclear binding of κB and transcription of pro-inflammatory cytokines. MMF also inhibits NF-κB via agonism of the hydroxycarboxylic acid receptor 2 (HCAR2) and antagonism of Toll-like receptors (TLRs) on the membrane. Fumarate causes metabolic shifts by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, and therefore, glycolysis. Fumarate enters mitochondria via the malate-aspartate shuttle, where it is ultimately sequestered into the matrix Krebs cycle and is completely metabolized to yield ATP and CO₂.