The mutation that made us citrus-dependent
Most mammals synthesize their own vitamin C. A 70 kg dog produces ~3,000 mg of ascorbic acid per day in its liver. Humans produce exactly zero milligrams of endogenous vitamin C. The gene encoding L-gulonolactone oxidase (GULO) — the enzyme catalyzing the final step of ascorbic acid synthesis — has been a non-functional pseudogene in the human genome for ~61 million years.
Structure: an enediol lactone with a reducing vocation
Ascorbic acid (C₆H₈O₆) is a γ-lactone with an enediol system at C-2 and C-3: two adjacent –OH groups at a C=C double bond. This system is the source of all its chemistry. The –OH at C-3 (pKa = 4.17) is unusually acidic — the charge is stabilized by resonance with the enediol and lactone carbonyl. At physiological pH (7.4), ascorbic acid exists almost entirely as the ascorbate anion (−1 charge).
Two-step oxidation: Ascorbate → radical semidehydroascorbate → dehydroascorbate (DHA). The intermediate radical is unusually stable — delocalized over the enediol — making it a chain-terminator rather than a chain-initiator.
Three essential functions
Collagen synthesis: Cofactor for prolyl and lysyl hydroxylases. Without ascorbate, Fe²⁺ in the active site oxidizes to Fe³⁺ and cannot be reduced back. Without hydroxyproline and hydroxylysine, the collagen triple helix cannot form correctly → scurvy (bleeding gums, non-healing wounds, tooth loss).
Non-heme iron absorption: Vitamin C reduces Fe³⁺ (poorly absorbed) to Fe²⁺ (transported by DMT-1). Simultaneous vitamin C source with iron-rich vegetarian food increases non-heme iron absorption 2–4 times.
Aqueous antioxidant and vitamin E regenerator: Vitamin C is the primary aqueous antioxidant in plasma. Oxidized vitamin E radical (tocopheroxyl radical) migrates to the membrane-water interface, where ascorbate reduces it back to active tocopherol — a coordinated antioxidant cycle protecting both aqueous and lipid phases.