The electrophilic carbon on sulforaphane, short of electrons, hits electron-rich targets and sticks covalently, and the richest target in a cell is the sulfur on cysteine.Sulforaphane carries an isothiocyanate group —N=C=S. The central carbon, drained of electrons by flanking N and S, is electrophilic: it hunts electron-rich targets and sticks covalently, though the bond is reversible and can come apart again. The richest target in a cell is the sulfur on cysteine.
2 · What it hits is a sensor
Normally KEAP1 keeps handing the transcription factor Nrf2 to the protein-disposal machine, so Nrf2 is dismantled as fast as it is built and its defense genes stay low.KEAP1 carries a row of cysteines and acts as a bridge: one end is Cul3 ubiquitin ligase (the protein-disposal machine), the other holds Nrf2, continuously handing it over for destruction. So Nrf2 is dismantled as fast as it is built; its level stays low, and the defense genes it controls stay low. This is a loaded spring, held down by a hand.
3 · The hand lets go
Once sulforaphane covalently modifies the cysteines of KEAP1, Nrf2 is no longer destroyed, builds up, enters the nucleus and transcribes cytoprotective enzymes.Sulforaphane covalently modifies KEAP1 cysteines including Cys151; the bridge breaks. Nrf2 accumulates, enters the nucleus, pairs with small Maf proteins, binds the ARE (antioxidant response element), and transcribes cytoprotective enzymes: glutathione S-transferase, NQO1, heme oxygenase-1, and GCL — the rate-limiting enzyme of glutathione synthesis.
4 · Not extinguishers — a fire drill
Sulforaphane cleared no free radical for you; what it did was widen the rate-limiting valve on the machine that builds scavengers.The benefit is built by you — the plant only pressed a button. This is a fire drill, not a delivery of extinguishers: the drill is a nuisance, but afterward your fire-fighting capacity is genuinely higher. The Keap1-Nrf2 pathway is considered the most important pathway underlying dietary phytochemical benefits.