BIOSYNTHESIS OF TETRAHYDROBIOPTERIN BY DENOVO AND SALVAGE PATHWAYS IN ADRENAL-MEDULLA EXTRACTS, MAMMALIAN-CELL CULTURES, AND RAT-BRAIN INVIVO
BIOSYNTHESIS OF TETRAHYDROBIOPTERIN BY DENOVO AND SALVAGE PATHWAYS IN ADRENAL-MEDULLA EXTRACTS, MAMMALIAN-CELL CULTURES, AND RAT-BRAIN INVIVO
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DOI：
10.1073/pnas.80.6.1546
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
DUCH, DS
中科院分区：
文献类型：
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作者：
NICHOL, CA;LEE, CL;DUCH, DS
哺乳动物细胞和组织有 2 条生物合成四氢生物蝶呤 (BH4) 的途径：通过甲氨蝶呤不敏感的从头途径将 GTP 转化为 BH4，以及通过依赖二氢叶酸还原酶 (EC 1.5.1.3) 活性的蝶呤补救途径将墨蝶呤转化为 BH4。在缺乏二氢叶酸还原酶 (DUKX-B11) 的中国仓鼠卵巢细胞突变体中，BH4 的内源形成正常进行，但与亲代细胞不同，这些细胞或其提取物不会将墨蝶呤或 7,8-二氢生物蝶呤转化为 BH4。 KB 细胞[人表皮样癌]不含有可检测水平的 GTP 环化水解酶或 BH4，但含有二氢叶酸还原酶，很容易将墨蝶呤转化为 BH4，并且甲氨蝶呤完全阻止这种转化。在牛肾上腺髓质的上清液部分中，甲氨蝶呤完全抑制墨蝶呤向 BH4 的转化。同样，大鼠大脑体内的这种转化对甲氨蝶呤敏感。墨蝶呤和 7,8-二氢双蝶呤显然不进入 BH4 生物合成的从头途径，并且可能源自尚未表征的不稳定中间体。
Mammalian cells and tissues have 2 pathways for the biosynthesis of tetrahydrobiopterin (BH4): the conversion of GTP to BH4 by a methotrexate-insensitive de novo pathway and the conversion of sepiapterin to BH4 by a pterin salvage pathway dependent on dihydrofolate reductase (EC 1.5.1.3) activity. In a Chinese hamster ovary cell mutant lacking dihydrofolate reductase (DUKX-B11), endogenous formation of BH4 proceeds normally but, unlike the parent cells, these cells or extracts of them do not convert sepiapterin or 7,8-dihydrobiopterin to BH4. KB cells [human epidermoid carcinoma], which do not contain detectable levels of GTP cyclohydrolase or BH4 but do contain dihydrofolate reductase, readily convert sepiapterin to BH4 and this conversion is completely prevented by methotrexate. In supernatant fractions of bovine adrenal medulla, the conversion of sepiapterin to BH4 is completely inhibited by methotrexate. Similarly, this conversion in rat brain in vivo is methotrexate-sensitive. Sepiapterin and 7,8-dihydrobipterin apparently do not enter the de novo pathway of BH4 biosynthesis and may be derived from labile intermediates which have not yet been characterized.