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Tetrahydrobiopterin metabolism Tetrahydrobiopterin (BH 4 ) is a naturally occurring molecule that is an essential cofactor for several critical metabolic pathways, including those responsible for the production of monoamine neurotransmitters, the breakdown of phenylalanine, and the production of nitric oxide ( 4 is readily oxidized by reactive species, leading it to be destroyed in the disorders where oxidative stress is prominent such as ASD ( 4 related metabolic pathways or in the products of these pathways have been noted in some individuals with ASD, and the cerebrospinal fluid concentration of BH 4 has been reported to be depressed in some individuals with ASD ( 4 , to treat children with ASD ( Frye has shown that the ratio of serum citrulline-to-methionine is related to the BH 4 concentration in the cerebrospinal fluid, suggesting that abnormalities in both oxidative stress and nitric oxide metabolism may be related to central BH 4 deficiency ( 4 metabolism in children with ASD