6-Pyruvoyl-tetrahydropterin

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. 

Shintaku H, Niederwieser A, leimbacher W, Curtius HC (1988) Tetrahydrobiopterin deficiency assay for 6-pyruvoyl-tetrahydropterin synthase activity in erythrocytes, and detection of patients and heterozygous carriers. Eur J Pediatr 147 15-19... 

Pyrovoyl tetrahydropterin synthetase catalyzes the second step in the conversion of guanosine triphosphate into tetrahydrobiopterin. The substrate, 4,8-dihydroneopterin triphosphate, is converted to 6-pyruvoyl tetrahydropterin. 

Figure 9.150 HPLC profiles of incubation mixtures for 6-pyruvoyl tetrahydropterin synthetase assays with extracts of (A) T 24 cells, (B) human dermal fibroblasts, and (C) a reagent control. Amounts of 56 fig (A) and 60 fig (B) of cellular protein or phosphate-buffered saline (C) were used in the assay. Incubation time was 70 minutes at 37°C. A 100 fiL aliquot of the incubation mixture was used. Fluorescence detection was at an excitation wavelength of 353 nm and an emission wavelength of 438 nm. Peaks 1, neopterin 2, biopterin. (From Warner et al., 1991.)...

Figure 3 Coenzymes biosynthesized from GTP. 8, molybdopterin 22, GTP 23, 5-amino-6-ribitylamino-2,4(1 H,3H)-pyrimidinedione 24, riboflavin 25, FMN 26, 5,6-dimethylbenzimidazole 27, precursor Z 28, metal containing pterin 29, dihydroneopterin triphosphate 30, 6-pyruvoyl-tetrahydropterin 31, 6(R)-5,6,7,8-tetrahydrobiopterin 32, dihydroneopterin 33, 6(S)-5,6,7,8-tetrahydrofolate 34, 5,6,7,8-tetrahydromethanopterin 35, 5-deaza-7,8-didemethyl-8-hydroxyribo-flavin 36, coenzyme F42q-...

The 1.25 A-crystal structure of the mouse SR in complex with NADP has been solved. The 261 amino acids of the monomer fold into a single domain a//3-structure. A seven-stranded parallel /3-sheet in the center of the molecule is sandwiched by two arrays of three a-helices. The association of two monomers to the active homodimeric SR leads to the formation of a four-helix bundle (Figure 13). Owing to the two-folded crystallographic symmetry of the homodimeric molecule, the parallel /3-sheets in monomer A is in an antiparallel orientation relative to the /3-sheet of monomer B enclosing an angle of 90°. The overall dimensions of the SR dimer are 40 A X 50 A x 80 A. The two substrate pockets bind sepiapterin (or 6-pyruvoyl-tetrahydropterin 42), and the cofactor NADP/NADPH from opposite sides to the enzyme. 

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