Vitamin C of mannose or galactose to ascorbic acid. In animals, the starting material is glucose. In some species that synthesize ascorbate in the liver (including mammals and perching birds), the glucose is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process. In animals that cannot synthesize vitamin C, the enzyme -gulonolactone oxidase (GULO), that catalyses the last step in the biosynthesis, is highly mutated and non-functional. The biosynthesis of ascorbic acid in vertebrates starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD
Vitamin C efficiency decreases as amounts increase. Intravenous administration bypasses this. Doing so makes it possible to achieve plasma concentrations of 5 to 10 millimoles/liter (mmol/L), which far exceed the approximately 0.2 mmol/L limit from oral consumption. The theories of mechanism are contradictory. At high tissue concentrations ascorbic acid is described as acting as a pro-oxidant, generating hydrogen peroxide (HO) to kill tumor cells. The same literature claims that ascorbic acid acts as an antioxidant, thereby reducing the adverse effects of chemotherapy and radiation therapy. Research continues in this field, but a 2014 review concluded: "Currently, the use of high-dose intravenous vitamin