Chemistry and Biochemistry of Vitamin C in Mammalian Systems

In most mammals, ascorbic acid (vitamin C) is synthesized in the liver, but humans and some other species have lost this capacity, and for them it is an essential nutrient. At physiologic pH, ascorbic acid is mostly present as the ascorbate anion and is a versatile electron donor that can act as an efficient free radical scavenger, with the resulting formation of the relatively stable ascorbyl (monodehydroascorbate) radical. It is also a reducing agent for transition metals such as Cu²⁺ and Fe³⁺, and together these properties form the basis of its biological activity. Oxidation leads to the formation of dehydroascorbate (DHA), a product that can be regenerated to reduced ascorbate but which also readily undergoes hydrolysis to irreversible degradation products. The transition metal-reducing capability of ascorbate promotes the activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs) and numerous monooxygenases by maintaining the active site Fe²⁺ or Cu⁺. In addition, ascorbate can have a pro-oxidant role, enabling hydrogen peroxide and Fe⁺-dependent hydroxyl radical production. Its iron-reducing capacity is also thought to contribute to the uptake of dietary iron.