Development of the pteridine pathway in the zebrafish, Danio rerio

In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either t o the cofactor tetrahydrobiopterin or to xanthophore pigments. The componen ts of the pteridine pattern were identified as tetrahydrobiopterin, sepiapt erin, 7-oxobiopterin, isoxanthopterin, and 2,4,7-trioxopteridine. The expre ssion of GTP cyclohydrolase I activity during the first 24-h postfertilizat ion, followed by 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase and sepiapter in reductase, suggest an early supply of tetrahydrobiopterin for neurotrans mitter synthesis in the neurons and for tyrosine supply in the melanophores . At 48-h postfertilization, sepiapterin formation branches off the de novo pathway of tetrahydrobiopterin synthesis, Sepiapterin, via 7,8-dihydrobiop terin and biopterin, serves as a precursor for the formation of 7-oxobiopte rin, which may be further catabolized to isoxanthopterin and 2,4,7-trioxopt eridine, Neither 7,8-dihydrobiopterin nor biopterin is a substrate for xant hine oxidoreductase. In contrast, both of these compounds are oxidized at C -7 by a xanthine oxidase variant form, which is inactivated by KCN, but is insensitive to allopurinol. The oxidase and the dehydrogenase form of xanth ine oxidoreductase as well as the xanthine oxidase variant have specific de velopmental patterns. It follows that GTP cyclohydrolase I, the formation o f sepiapterin, and the xanthine oxidoreductase family control the pteridine pathway in the zebrafish.