Collagen's strength depends on hydroxylated proline and lysine residues. Prolyl hydroxylase and lysyl hydroxylase insert an -OH group onto these residues, and both enzymes require ascorbate as a reducing cofactor. The reaction consumes ascorbate while converting an iron atom in the enzyme's active site back to its Fe(II) state, which is the form that binds molecular oxygen and the substrate. Without ascorbate, the iron oxidizes to Fe(III), the enzyme stalls, and proline and lysine remain unhydroxylated. Unhydroxylated collagen cannot form the hydrogen bonds that stabilize the triple helix, so the molecule is unstable and is degraded rather than secreted. The result is weak connective tissue: blood vessel walls that leak, gums that bleed, skin that fails to heal, and wounds that reopen. This is the molecular basis of scurvy.
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Ascorbate as the Cofactor for Collagen Hydroxylation
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Look at the enzyme active site. The iron must stay in the Fe two plus state for the hydroxylase to work. Ascorbate donates an electron to restore that state after each catalytic cycle. When ascorbate is missing, the iron drifts to Fe three plus, the enzyme stops, and proline and lysine are never hydroxylated. Follow the collagen strand on the right: without those hydroxyl groups, the three chains cannot hydrogen-bond into a stable triple helix, so the molecule is degraded instead of secreted. That is why the first symptoms appear in tissues that depend on strong collagen: vessel walls, gums, skin, and healing wounds.
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