L-Sepiapterin

Diamino-6-hydroxypyrimidine, 6R-5,6,7,8-tetrahydro-L-biopterin and L-sepiapterin were potent inhibitors of the recombinant interferon-y-induced production of nitrogen oxides in intact cultured rat alveolar macrophages with I50 values for 6R-5,6,7,8-tetrahydro-L-biopterin and L-sepiapterin of approximately 10 pM (Jorens et al. 1992). 

Sheng, J. Wang, D. Braun, A. P. DAF-FM (4-amino-5-methylamino-2, 7 -difluorofluorescein) diacetate detects impairment of agonist-stimulated nitric oxide synthesis by elevated glucose in human vascular endothelial cells Reversal by vitamin C and L-sepiapterin. J. Pharmacol. Exp. Then 2005, 315, 931-940. 

Another unusual rearrangement is performed by Bacillus subtilis during the catabolism of sepiapterin (237), in converting the whole side-chain with subsequent oxidation of the pyrazine ring into 6-(l-carboxyethoxy)pterin (238 equation 75). 

Bonafe L, Thony B, Penzien JM, Czarnecki B, Blau N (2001) Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet 69 269-277... 

Blau N, Bonafe L, Thony (2001) Tetrahydrobiopterin deficiencies without hyperphenyl-alaninemia diagnosis and genetics of Dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab 74 172-185... 

Enzymatic reactions in the side chains of pteridines are recommended for such cases where the chemical transformations are difficult and nonselective. A convincing example of this approach is the enzymatic isomerization of sepiapterin (6-lactoyl-7,8-dihydropterin) (297) into 6-(l-hydroxy-2-oxopropyl)-7,8-dihydropterin (298) which had been believed to be too labile to actually exist (Equation (13)) <89MI 718-06). This product, which was formed by the isomerase activity of sepiapterin reductase, was detectable electrochemically at 500 mV and fluorometrically on HPLC analysis. 

These oxidation reactions require oxygen (O2) and tetrahydrobiopterin as a cofactor. Thus, as shown in Scheme 13.39, 7,8-dihydroneopterin 3 -triphosphate (generated from guanosine triphosphate [GTP] as seen in Scheme 12.118) is converted to 6-pyruvoyl-5,6,7,8-tetrahydropterin by an elimination reaction and two keto-enol isomerizations. The process is catalyzed by the enzyme 6-pyruvoyltetra-hydropterin synthase (EC 4.2.3.12). Then, via an intermediate, written as an equilibrium between a-hydroxyketones (named dihydrosepiapterin) linked by a common enol, reduction to tetrahydrobiopterin is effected (in two separate steps) by 2 equivalents of NADPH used by the enzyme sepiapterin reductase (EC 1.1.1.153). Tetrahydrobiopterin is the cofactor involved in the National Institutes of Health (NIH) shift (cf. Chapter 6) pathway used by the iron-containing enzyme phenylalanine 4-monooxygenase (EC 1.14.16.1) to convert phenylalanine (Phe, F) to tyrosine (Tyr, Y) and is converted to (6i )-6-(L-erythro-l,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin in the process. 

Senecio spp., 1384, 1553 Seneciphylline, 1061, 1062, 1178, 1386 Senegin III, 3217 Senile plaques, 3712, 3716 Sensitivity enhancement, 1105 Sensory analysis, 2267 Sensory characteristic, 2906 Sensory perception, 2264 Sepiapterin reductase, 1209 Sepsis, 1306 S-Eq producers, 2402 Sequence tags, 2954 S-equol (5-Eq), 2398 SERCA, 3077, 3090, 3091, 3093, 3095 Sergeolide, 3778 L-Serine, 942 Serine protease, 987, 988 Serjania meridionalis, 4094 Serotonergic (5-HT), 3709, 3711 neurons, 1516 system, 1309 Serotonin, 598, 686, 4068 Serpentine, 1126 Sertiiumer, 1368,1373 Sesame oil, 4065 Sesamin, 4065... 

Fig. 1.1. Biosynthesis and regeneration of tetrahydrobiopterin including possible metabolic defects and catabolism of phenylalanine. l.l=phenylalanine-4-hydroxylase (PAH) 1.2/1.6 = GTP cyclohydrolase I (GTPCH), 1.3 = 6-pyruvoyl-tetra-hydropterin synthase (PTPS), 1.4 = dihydropteridine reductase (DHPR), 1.5 = pterin-4a-carbinolamine dehydratase (PCD), 1.7 = sepiapterin reductase SR, carbonyl reductase (CR), aldose reductase (AR), dihydrofolate reductase (DHFR), aromatic amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), nitric oxide synthase (NOS). Pathological metabolites used as specific markers in the differential diagnosis are marked in squares. n.e.=non-enzymatic...

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