Vitamin C (Ascorbic Acid)

Mechanism

Mechanism of enzymatic action

Ascorbic acid acts as an electron donor for metalloenzymes containing iron or copper cations, maintaining them in their catalytically active reduced state (Fe²⁺ and Cu⁺):

1. Collagen Hydroxylation: Acts as a cofactor for the mitochondrial prolyl hydroxylase and lysyl hydroxylase enzymes. These enzymes add hydroxyl groups to the proline and lysine residues of procollagen, allowing cross-linking and intermolecularization that stabilizes the triple helix structure of mature collagen.
2. Catecholamine Synthesis: Necessary for the enzyme dopamine β-hydroxylase, which converts dopamine to noradrenaline in synaptic vesicles.
3. Carnitine Synthesis: Cofactor in the hydroxylations of the carnitine synthesis pathway, a mitochondrial transporter of fatty acids.

The reversible autoxidation of ascorbate to dehydroascorbate proceeds according to:

Cellular Dehydroascorbate Recycling

Inactive oxidized dehydroascorbate is rapidly taken up by cellular facilitatory glucose transporters (GLUT-1 and GLUT-3) and internalized. In the cellular cytosol, it is reduced back to active ascorbate by the enzyme dehydroascorbate reductase with expenditure of cellular glutathione (GSH), maintaining tissue antioxidant defenses.

Security

Clinical Indications, ADRs and Interactions

• Prevention and Treatment of Scurvy: Clinically manifested by severe capillary fragility (petechiae, spontaneous gingival bleeding with loss of teeth), severe delay in wound healing, generalized bone pain and weakness of tissue connective tissue.
• Adjuvant treatment to improve Iron Absorption: It is administered together with oral ferrous sulfate to maintain the cation in a soluble ferrous state in the intestinal lumen.
• Excess ADRs: Chronic megadoses of vitamin C (> 2 g/day) undergo metabolism and cleavage into free oxalate in the kidney, significantly increasing the risk of nephrolithiasis due to calcium oxalate crystals in the gastric urinary tract.