Sepiapterin

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). 

For the synthesis of drosopterin, tetrahydrobiopterin, sepiapterin, 7-oxopterin and isoxanthopterin, DHN-TP is first converted to the common intermediate 6-pyruvoyl-tetrahydropterin. The biosynthesis of pteridines was studied in zebrafish in relation with the differentiation of neural crest derivatives. The key intermediate in the synthesis of 7-oxobiopterin is the sepiapterin. Pteridins are produced in xanthophores and erythrophores of fish and amphibian species. 

Purines absorb only ultraviolet light and they contribute to structural colors (white and silver) in animals. Pterines are generally yellow, orange, or red pigments. Because they are amphoteric molecules, the absorption spectra depend on the pH and present three or two absorption maxima, usually one in the visible region. Sepiapterin has an absorption maximum at 340 nm in O.IM NaOH and at 410 nm in O.IM HCl." Leucopterin has three maxima 240, 285, and 340 nm. Xanthopterin has two 255 and 391 nm. Because they are conjugated with proteins, pterins show bathochromic shifts in vivo. They also present fluorescence when excited with UV light. 

In rare instances, PKU is caused by defects in the metabolism of BH4, which is synthesized from GTP via sepiapterin (Fig. 40-2 reactions 3 and 4) [25]. Even careful phenylalanine restriction fails to avert progressive neurological deterioration because patients are unable to hydroxylate tyrosine or tryptophan, the synthesis of which also requires tetrahydrobiopterin. Thus, neurotransmitters are not produced in sufficient amount. 

The silkworm, Bombyx mori (Bombycidae), contains in various body parts simple alkylamines, tryptophan metabolites, and pteridines (Tables V, VI, and VIII). One of the pteridines, violapterin (78), is synthesized from isoxanthopterin (67) by isoxanthopterin deaminase, occurring in the larvae and adults, and is stored in situ in the larval and adult integument (80). In addition, sepiapterin deaminase in the integument of the lemon mutant silkworm catalyzes the deamination of sepiapterin (81) to 7,8-dihydro-6-lactyllumazine (79) (81). 

There are a number of studies on the biosynthesis of various pteridines, i.e., xanthopterin (65), isoxanthopterin (67), erythropterin (73), leucopterin (68), and pterin (62) (509-511). The most important intermediate of the proposed biosynthetic pathway from guanosine triphosphate (GTP) (604) seems to be di-hydroneopterin triphosphate (H2-NTP) (605), however, because evidence has recently been accumulated indicating that pteridines such as biopterin (70), sepiapterin (81), and drosopterins (87) are synthesized from GTP (604) by way of H2-NTP (605) (Scheme 76) (5/2). 

Biosynthetic pathways of sepiapterin (81) and drosopterins (87) were recently... 

The putative E. coli gene of the 6-pyruvoyltetrahydropterin synthase (PTPS) was cloned and overexpressed in order to identify the enzymatic activity to synthesize 6-pyruvoyltetrahydropterin from dihydroneopterin triphosphate <2002MI234>. The protein was shown to have another new catalytic function to convert sepiapterin to 7,8-dihydroneopterin. 

Pipette 0.2 ml of CSF or amniotic fluid into an Ultrafree 10000 Filter Unit (Millipore), add 40 pi of water, 30 pi of 30% (w/v) TCA, and 1 mg of Mn02 (see above) shake for 5 min at room temperature. Centrifuge for 30 min at 2000 xg. Immediately transfer the clear supernatant into a vial. For sepiapterin determination, samples should be analyzed without oxidation. 

Sepiapterin stock solution (100 pM) dissolve 2.36 mg sepiapterin in 100 ml degassed and nitrogen-washed double-distilled water. Store aliquots at -20°C. 

Sepiapterin working solution (200 nM) Dilute 1 ml of 100 pM stock solution with water (degassed and nitrogen-washed double-distilled water) and mix 1 ml of this solution (lpM) with 4 ml of water (degassed and nitrogen-washed double-distilled water). Store aliquots at -20°C. 

Fig. 6.1.8a-c HPLC of the yellow-fluorescing pterins, a Standard mixture b control cerebrospinal fluid (CSF) c CSF sepiapterin reductase deficiency. HS -Hydroxyse-piapterin, S sepiapterin, X xanthopterin... 

Table 6.1.5 Reference values for pterins in urine, serum, and cerebrospinal fluid. Bio biopterin, CSF cerebrospinal fluid, Neo neopterin, S serum, Sep sepiapterin, U urine...

DHPR Dihydropteridine reductase, DRD dopa-responsive dystonia, GTPCH GTP cyclohydrolase I, n normal, PCD pterin-4a-carbinolamine dehydratase, PTPS 6-pyruvoyltetrahydrobiopterin synthase, SR sepiapterin... 

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... 

Sueoka T, Katoh S (1982) Purification and characterization of sepiapterin reductase from rat erythrocytes. Biochim Biophys Acta 717 265-271... 

Citron BA, Milstien S, Gutierrez JC, Levine RA, Yanak BL, Kaufman S (1990) Isolation and expression of rat liver sepiapterin reductase cDNA. Proc Natl Acad Sci U S A 87 6436-6440... 

Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (1991) Cloning and sequencing of cDNA encoding human sepiapterin reductase - an enzyme involved in tetrahydrobiop-terin biosynthesis. Biochem Biophys Res Commun 179 183-189... 

Ferre J, Naylor EW (1988) Sepiapterin reductase in human amniotic and skin fibroblasts, chorionic villi, and various blood fractions. Clin Chim Acta 174 271-282... 

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... 

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