A free radical steals an electron from a polyunsaturated fatty acid in the cell membrane, which becomes a new radical and sets off a chain reaction.A free radical is a molecule with unpaired electrons — chemically highly unstable, grabbing electrons wherever it sees them. The mitochondrial respiratory chain leaks ~ 1-2% of oxygen molecules daily as superoxide (•O₂⁻); UV, radiation, tobacco, and chronic inflammation all increase production.
The most dangerous is •OH (hydroxyl radical) — half-life < 1 nanosecond, extreme reactivity, destroys whatever it touches.
It prefers to attack the polyunsaturated fatty acid tails () of the cell membrane (e.g. 's 6 double bonds) — once PUFA loses an electron, it itself becomes a new radical → chain reaction (lipid peroxidation). One radical can destroy hundreds to thousands of membrane lipid molecules.
2 · Vitamin E intercepts
Vitamin E (α-tocopherol) is lipid-soluble — it lives inside the membrane, embedded among phospholipid tails, as the membrane's personal bodyguard.When a free radical tries to grab a electron, the -OH on E jumps in first, donating a hydrogen atom (H•, one proton + one electron) to the radical —
· The radical is neutralised ← gets the electron, becomes stable · E itself becomes a tocopheryl radical (α-TO•) — now E becomes a radical itself, but because its phenol ring structure can delocalise electrons, it's ~ 10⁵ × more stable than a lipid radical — won't initiate chain reactions
This is why E can intercept the peroxidation cascade — it lowers the reactivity of the radical, rather than eliminating it. But now it's useless until reduced back.
3 · Vitamin C restores E
Vitamin C (ascorbate) is water-soluble — it lives in cytoplasm + plasma, contacting membrane-bound E at the lipid membrane's aqueous interface.C gives E an electron:
· E activity is restored → re-embeds in the membrane, returns to duty · C itself becomes the ascorbyl radical (Asc•⁻) → loses another electron → dehydroascorbate (DHA)
This is the chemical root of C reduces E back — C's role isn't to directly neutralise membrane radicals; it's to repair E so E can keep neutralising.
Electron flow across membrane sides: lipid phase (E) → aqueous phase (C) → this is exquisitely engineered cross-boundary collaboration.
But C is now DHA and useless until someone reduces it back.
4 · GSH closes the loop
Two glutathione molecules reduce spent vitamin C back, glutathione is then restored by , so C, E and GSH are recycled and what is really consumed is NADPH.Glutathione (GSH) is the most abundant small-molecule antioxidant in the cell (~ 1-10 mmol/L) — a tripeptide of Cys, Glu, Gly, with the active site being the sulfhydryl (-SH) on Cys.
Two GSH collaborate to reduce dehydroascorbate (DHA) back to C:
2 GSH + DHA → GSSG + ascorbate
· Each GSH loses one H → forms a disulfide bond, becoming oxidised GSSG · C fully restored → re-enters the cycle
GSSG can also be reduced back: GSSG + → 2 GSH (by glutathione reductase, NADPH from the pentose phosphate pathway).
Whole system: free radical → neutralised; E, C, GSH are three rotating recycled components, not consumed — what's actually consumed is NADPH (i.e. the energy from glucose metabolism).
This is the chemical closed loop of C · E · GSH antioxidant trio. Supplementing just one alone has limited meaning; coordinated turnover is normal physiology.
Practical implications: · Balanced food intake of C (fresh fruits / veg) + E (nuts / seeds / oils) + GSH precursors (sulphur-containing amino acids: eggs / meat / cruciferous veg) > any single mega-dose supplement · Mega-dose C when GSH system is poor → C can paradoxically become pro-oxidant (Fenton reaction releasing Fe²⁺ generating •OH) — this is why mega-dose C trials are generally negative