AUTHOR=Frye Richard E. TITLE=Central tetrahydrobiopterin concentration in neurodevelopmental disorders JOURNAL=Frontiers in Neuroscience VOLUME=4 YEAR=2010 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2010.00052 DOI=10.3389/fnins.2010.00052 ISSN=1662-453X ABSTRACT=

Tetrahydrobiopterin (BH4) is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH4 supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH4 concentration and systemic metabolism and to develop a biomarker of central BH4 concentration, the relationship between cerebrospinal fluid BH4 concentration and serum amino acids was studied. BH4 concentration was found to be distributed in two groups, a lower and higher BH4 concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH4 concentration (r = −0.67, p < 0.05). Both citrulline and methionine are substrates in inflammation and oxidative stress pathways – two pathways that utilize BH4 and are abnormally activated in autism. These data suggests that central BH4 concentration may be related to systemic inflammation and oxidative stress pathways.