Curtius H C, Matasovic A, Schoedon G, Kuster T, Guibaud P, Giudici T, Blau N
Department of Pediatrics, University of Zurich, Switzerland.
J Biol Chem. 1990 Mar 5;265(7):3923-30.
Three novel pteridines have been isolated from the urine of patients with a new variant of 6-(L-erythro-1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin (tetrahydrobiopterin) deficiency, showing hyperphenylalaninemia. From the results of high performance liquid chromatography, oxidative degradation, and gas chromatography-electron impact mass spectrometry, their structures were identified as 7-(D-erythro-1',2',3'-trihydroxypropyl)-pterin (7-neopterin), 7-(L-erythro-1',2'-dihydroxypropyl)-pterin (7-biopterin), and 6-oxo-7-(L-erythro-1',2'-dihydroxypropyl)-pterin (6-oxo-7-biopterin). The ratio of biopterin to 7-biopterin in the patients' urines was 1:1, and after oral loading with tetrahydrobiopterin, 7-biopterin excretion rose parallel to biopterin. This finding suggests that 7-substituted pterins may be formed endogenously by a yet unknown isomerization reaction. The cause of hyperphenylalaninemia is still unclear. The activities of the enzymes involved in tetrahydrobiopterin biosynthesis and regeneration were found to be normal in the patients, and no effect of 7-biopterin on these enzymes was observed in vitro. However, compared with the normal cofactor, tetrahydrobiopterin, the Km values of tetrahydro-7-biopterin for phenylalanine hydroxylase and dihydropteridine reductase are 20 and 5 times higher, respectively.
从患有一种新型6-(L-赤藓糖-1',2'-二羟基丙基)-5,6,7,8-四氢蝶呤（四氢生物蝶呤）缺乏症且伴有高苯丙氨酸血症的患者尿液中分离出了三种新型蝶啶。通过高效液相色谱、氧化降解以及气相色谱-电子轰击质谱分析的结果，确定了它们的结构分别为7-(D-赤藓糖-1',2',3'-三羟基丙基)-蝶呤（7-新蝶呤）、7-(L-赤藓糖-1',2'-二羟基丙基)-蝶呤（7-生物蝶呤）和6-氧代-7-(L-赤藓糖-1',2'-二羟基丙基)-蝶呤（6-氧代-7-生物蝶呤）。患者尿液中生物蝶呤与7-生物蝶呤的比例为1:1，口服四氢生物蝶呤后，7-生物蝶呤的排泄量与生物蝶呤平行上升。这一发现表明，7-取代蝶呤可能通过一种未知的异构化反应内源性形成。高苯丙氨酸血症的病因仍不清楚。发现参与四氢生物蝶呤生物合成和再生的酶活性在患者中正常，并且在体外未观察到7-生物蝶呤对这些酶有影响。然而，与正常辅因子四氢生物蝶呤相比，四氢-7-生物蝶呤对苯丙氨酸羟化酶和二氢蝶啶还原酶的Km值分别高20倍和5倍。
