Biopterin

Biopterin
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生物蝶呤

DOI:
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发表时间:
1978
影响因子:
4.4
通讯作者:
Sherman Ad
Sherman Ad
中科院分区:
医学3区
文献类型:
--
作者:
Gál Em;Nelson Jm;Sherman Ad

文献摘要

被引文献

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三种特定的酶参与了大脑从GTP合成7,8-二氢生物蝶呤的过程。对这些细胞进行了分离、纯化和鉴定。第一个酶也催化限速步骤,是GTP环水解酶A-I或依赖于镁的A-II,它将GTP水解成特定的产物2-amino-6-(5-triphosphoribosyl)-amino-5-or-6-formamido-6-hydroxypyrimidine(Fpyd-P3)。FPYD-P3是由一种合成酶--赤藓-7,8-二氢蝶呤三磷酸(NPTH2-P3)环化的。新的酶D-赤藓-7,8-二氢蝶呤三磷酸合成酶(酶B)是一种9177道尔顿的碱性蛋白,含有三个自由的SH基团,N-异亮氨酰丝基-AS和Valyl-谷氨酰基-AS C-末端。这种酶由大鼠的69个氨基酸残基和豚鼠脑的68个氨基酸残基(少一个天冬氨酸)组成,不含羟脯氨酸、蛋氨酸或色氨酸。大鼠脑中的酶会逐渐将其产物NPTH2-P3转化为BH2,而豚鼠脑中的酶则缺乏这一特性。2,4-氨基-6-羟基嘧啶和dFPyd-P3是该酶的有效抑制剂。7,8-二氢生物蝶呤合成酶(C酶)催化NPTH2-P3合成BH2,而不是由7,8-二氢蝶呤合成BH2。这种酶不需要吡啶核苷酸或镁离子来催化。
Three specific enzymes are involved in the cerebral synthesis of 7,8-dihydrobiopterin from GTP. These were isolated, purified, and characterized. The first enzyme, also catalyzing the rate-limiting step, is GTP-cyclohydrolase A-I or Mg2+-dependent A-II, which hydrolyze the GTP to the specific product 2-amino-6-(5-triphosphoribosyl)-amino-5-or-6-formamido-6-hydroxypyrimidine (FPyd-P3). FPyd-P3 is cyclized by a synthetase tod-erythro-7,8-dihydroneopterintriphosphate (NPTH2-P3). The new enzyme,d-erythro-7,8-dihydroneopterintriphosphate synthetase (enzyme B) is a basic protein of 9177 daltons containing three free SH groups, isoleucyl-seryl- as N- and valyl-glutamyl- as C-terminals. This enzyme of 69 amino acid residues from rat and 68 residues (one less aspartic acid) from guinea pig brain contains no hydroxyproline, methionine, or tryptophan. The enzyme from rat brain will gradually convert its product NPTH2-P3 to BH2, whereas the enzyme from guinea pig brain lacks this property. 2,4-amino-6-hydroxypyrimidine and dFPyd-P3 are effective inhibitors of this enzyme. The synthesis of BH2 from NPTH2-P3, but not from 7,8-dihydroneopterin, is catalyzed byl-erythro-7,8-dihydrobiopterin synthetase (enzyme C), which was purified to electrophoretic purity. This enzyme does not require pyridine nucleotides or Mg2+ for its catalysis.