Tetrahydrobiopterin and biogenic amine metabolism in neuropsychiatry, immunology, and aging.

Tetrahydrobiopterin (BH4) is essential for biogenic amine synthesis, and alterations in its metabolism occur at birth (atypical PKU), in neuropsychiatric illnesses, and in aging. BH4 therapy has been attempted in atypical PKU and in neuropsychiatric illness with some success and may become more viable as more is learned about BH4 metabolism and ways are discovered to elevate brain BH4 levels. It is intriguing to consider that a genetic defect in BH4 biosynthesis occurring at birth might go unrecognized and contribute to altered biogenic amine metabolism that occurs in neuropsychiatric illness. Since there seems to be a sensitivity of BH4 metabolism to genetic alterations, it is possible that altered BH4 metabolism is involved in some of deleterious effects associated with the aging process. A link between genetic alterations in BH4 metabolism at birth and adult neuropsychiatric illness and aging remains to be established, although this seems plausible. The presence of BH4 and other pterins in cells of the immune system as well as the pineal gland and other neuroendocrine tissues suggests the potential for other functions of pterins. Hopefully, future research will uncover the full potential for the therapeutic use of BH4 in a variety of diseases as well as elucidating other potential roles for pterin molecules which are present in many different systems.