Cerebrospinal fluid nitrite plus nitrate correlates with tetrahydrobiopterin concentration

Within the central nervous system (CNS), tetrahydrobiopterin (BH sub(4)) is an essential cofactor for the aromatic amino acid monoxygenases. Consequently, inborn errors of BH sub(4) metabolism result in hyperphenylalaninaemia and impaired dopamine and serotonin metabolism. Furthermore, the intracell...

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Bibliographic Details
Published in:Journal of inherited metabolic disease 1999-05, Vol.22 (3), p.221-223
Main Authors: Heales, S. J. R., Canevari, L., Brand, M. P., Clark, J. B., Land, J. M., Hyland, K.
Format: Article
Language:English
Subjects:
Adolescent
Aminoacid disorders
Biological and medical sciences
Biopterins - analogs & derivatives
Biopterins - cerebrospinal fluid
Child
Child, Preschool
Errors of metabolism
Humans
Infant
Infant, Newborn
Medical sciences
Metabolic diseases
Nitrates - cerebrospinal fluid
Nitrites - cerebrospinal fluid
tetrahydrobiopterin
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Summary:Within the central nervous system (CNS), tetrahydrobiopterin (BH sub(4)) is an essential cofactor for the aromatic amino acid monoxygenases. Consequently, inborn errors of BH sub(4) metabolism result in hyperphenylalaninaemia and impaired dopamine and serotonin metabolism. Furthermore, the intracellular BH sub(4) concentration may regulate the rate of aromatic amino acid hydroxylation due to the relatively high K sub(m) ( mu mol/L) of the aromatic amino acid monoxygenases for BH sub(4). Evidence for this in man comes from our observation that homovanillic acid, a dopamine metabolite, and 5-hydroxyindoleacetic acid, a serotonin metabolite, both exhibit a strong positive correlation with BH sub(4) in cerebrospinal fluid (CSF). We have postulated that an impaired ability to generate NO may be an important contributing factor to the neurological disturbances associated with BH sub(4) deficiency. To test this hypothesis, we have utilized the hph-1 mouse, which displays a well-characterized deficiency (-50%) of BH sub(4). Using this model, we have obtained data that suggest that NO generation is profoundly disturbed in the brains of these animal.
ISSN:0141-8955
1573-2665
DOI:10.1023/A:1005540828706