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The biosynthetic conversion of dihydroneopterin triphosphate (NH2P3) to tetrahydrobiopterin (BH4) is still unclear in its details. While earlier ~)rOPOSals favoured the involvement of sepiapterin as an intermediate (1,2,3), more recent work from several laboratories suggests that this is not the case, and that biosynthesis proceeds via tetrahydropterin interme­ diates (4-8). The conversion of NH2P3 to BH4 requires reduction with 4 electrons or 2 hydride equivalents (9); the latter are likely to originate from reduced pyridine nucleotides (7). Earlier studies from Krivi and Brown (10) dealt with the incorporation of label from (4S-3H)NADPH into sepiapterin. As also discussed elsewhere (9), the lack of stereospecifici­ ty in the incorporation of label into sepiapterin, and the probable nonin­ volvement of the latter in the biosynthesis (4-8), question the relevance of these (10) results.

BIOSYNTHESIS OF TETRAHYDROBIOPTERIN: INCORPORATION OF LABEL FROM REDUCED PYRIDINE NUCLEOTIDE DURING FORMATION FROM DIHYDRONEOPTERIN TRIPHOSPHATE