{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:41:04Z","timestamp":1788424864482,"version":"build-2803163510"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1991,1,15]]},"abstract":"<jats:p>A new variant form of hyperphenylalaninemia has recently been discovered in which the patients characteristically excrete 7-biopterin in their urines in addition to the natural 6-biopterin (Curtius, H. Ch., Kuster, T., Matasovic, A., Blau, N. &amp; Dhondt, J.-L. (1988) Biochem. Biophys. Res. Commun. 153, 715-721). This isomer had not been found previously in humans, and although its origin was not established, preliminary evidence suggested that it might be produced from 6-biopterin. We have now found that 7-biopterin can be formed in vitro from (6R)-tetrahydrobiopterin during the hydroxylation of phenylalanine catalyzed by phenylalanine hydroxylase [L-phenylalanine, tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1]. The resulting 7-biopterin was unequivocally identified by the following criteria: preparative isolation and conversion to 7-hydroxymethylpterin following periodate oxidation and borohydride reduction, quantitative conversion to pterin-7-carboxylic acid after oxidation with permanganate, and liquid chromatography\/thermospray mass spectrometry. Addition of 4a-carbinolamine dehydratase, an enzyme involved in the regeneration of tetrahydrobiopterin from the pterin carbinolamine intermediate (also called 4a-hydroxytetrahydrobiopterin) formed in the phenylalanine hydroxylase reaction, greatly decreased the amount of the 7-biopterin formed. This result implies that the in vitro formation of 7-biopterin occurs via the nonenzymatic rearrangement of the unstable substrate of the dehydratase, 4a-hydroxytetrahydrobiopterin, and suggests that this new variant of hyperphenylalaninemia may be caused by a lack of 4a-carbinolamine dehydratase activity. A mechanism for the rearrangement is proposed that predicts that other 6-substituted tetrahydropterin substrates of the aromatic amino acid hydroxylases could also give rise to rearranged products from an opening of the pyrazine ring of the corresponding 4a-hydroxytetrahydropterin intermediate.<\/jats:p>","DOI":"10.1073\/pnas.88.2.385","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:47:53Z","timestamp":1149061673000},"page":"385-389","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Conversion of 6-substituted tetrahydropterins to 7-isomers via phenylalanine hydroxylase-generated intermediates."],"prefix":"10.1073","volume":"88","author":[{"given":"M D","family":"Davis","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Milstien","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1991,1,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.88.2.385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:23:02Z","timestamp":1649856182000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.88.2.385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,1,15]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1991,1,15]]}},"alternative-id":["10.1073\/pnas.88.2.385"],"URL":"https:\/\/doi.org\/10.1073\/pnas.88.2.385","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,1,15]]},"assertion":[{"value":"1991-01-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}