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
L-gulonolactone oxidase deficiency living in a malarial infested environment". He based his observation on evidence which indicates that G6PD deficient individuals display enhanced sensitivity to ascorbic acid induced hemolysis. Studies of human diseases have benefited from the availability of small laboratory animal models. However, the tissues of animal models with a GULO gene generally have high levels of ascorbic acid and so are often only slightly influenced by exogenous vitamin C. Guinea pigs, for instance, are a popular human model but lost the ability to synthesize L-gulono-gamma-lactone oxidase 20 million years ago. This is a major handicap for studies involving the endogenous