title: Tetrahydro-sepiapterin is an intermediate in tetrahydrobiopterin biosynthesis.
abstract: 7,8-Dihydrobiopterin is not an intermediate in the de novo biosynthesis of tetrahydrobiopterin, the cofactor required for aromatic amino acid hydroxylations. However, N-acetyl-serotonin inhibition of sepiapterin reductase, an enzyme whose previously only known function was the reduction of sepiapterin to 7,8-dihydrobiopterin, completely inhibited biosynthesis of tetrahydrobiopterin by bovine adrenal medulla extracts. We have now shown that sepiapterin reductase catalyzes the reduction of tetrahydro-sepiapterin to tetrahydrobiopterin and that this reaction is N-acetyl-serotonin-sensitive. A new pathway for tetrahydrobiopterin biosynthesis is proposed which takes these observations into account and which involves tetrahydro intermediates.
mesh_terms: D000313:Adrenal Medulla / Q000201:enzymology; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis*; D002417:Cattle; D004926:Escherichia coli / Q000201:enzymology; D006136:GTP Cyclohydrolase / Q000378:metabolism; D007934:Leuconostoc / Q000201:enzymology; D008550:Melatonin / Q000494:pharmacology; D011621:Pteridines / Q000096:biosynthesis* / Q000378:metabolism*; D011622:Pterins; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D011621:Pteridines; D011622:Pterins; D001708:Biopterins; D012701:Serotonin; C039334:tetrahydrosepiapterin; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; D013762:Tetrahydrofolate Dehydrogenase; D006136:GTP Cyclohydrolase; C003402:sapropterin; D008550:Melatonin; C006389:N-acetylserotonin