Cerebrospinal fluid nitrite plus nitrate correlates with tetrahydrobiopterin concentration

摘要: Within the central nervous system (CNS), tetrahydrobiopterin (BH 4 ) is an essential cofactor for aromatic amino acid monoxygenases. Consequently, inborn errors of BH metabolism result in hyperphenylalaninaemia and impaired dopamine serotonin (Blau et al 1993). Furthermore, intracellular concentration may regulate rate hydroxylation due to relatively high K m (μmol/L) monoxygenases . Evidence this man comes from our observation that homovanillic acid, a metabolite, 5-hydroxyindoleacetic both exhibit strong positive correlation with cerebrospinal fluid (CSF) (Hyland Current treatment regimes often focus on phenylalanine restriction monoamine replacement therapy While strategy beneficial, it also be incomplete since significant number patients neurological impairment still apparent The exact reason failure not known but related other roles obligatory all isoforms nitric oxide synthase (Knowles Moncada 1994). In view key biochemical now attributed (NO), e.g. cGMP formation regulation glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Garthwaite Boulton 1995; Heales 1997), we have postulated ability generate NO important contributing factor disturbances associated deficiency. To test hypothesis, utilized hph-1 mouse, which displays well-characterized deficiency (-50%) (Brand 1995). Using model, obtained data suggest generation profoundly disturbed brains these animal, i.e. cerebellar synthesis whole-brain GAPDH activity increased 4-fold 1996; 1997). However, presence exogenous source NO, restored, suggesting via NOS 1996). order ascertain whether availability influences man, measured, (CSF), degradation products nitrite nitrate (Clelland 1996) tested concentration.