Tetrahydrobiopterin generate BH4 or BH3 radical and BH2, respectively. Research shows that ascorbic acid (also known as ascorbate or vitamin C) can reduce BH3 radical into BH4, preventing the BH3 radical from reacting with other free radicals (superoxide and peroxynitrite specifically). Without this recycling process, uncoupling of the endothelial nitric oxide synthase (eNOS) enzyme and reduced bioavailability of the vasodilator nitric oxide occur, creating a form of endothelial dysfunction. Ascorbic acid is oxidized to dehydroascorbic acid during this process, although it can be recycled back to ascorbic acid. Other than PKU studies, tetrahydrobiopterin has participated in clinical trials studying other approaches
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