Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence.
Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence.
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DOI：
10.1515/bc.2009.010
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发表时间：
2009-01
影响因子：
3.7
通讯作者：
Werner ER
中科院分区：
文献类型：
--
作者：
Watschinger K;Keller MA;Hermetter A;Golderer G;Werner-Felmayer G;Werner ER
甘油醚单加氧酶是一种四氢生物蝶呤依赖性的膜结合酶，其催化脂质醚裂解成甘油和相应的醛。尽管有许多不同的表征和纯化尝试，但迄今为止还没有基因和一级序列被分配给这种酶。其他七种四氢生物蝶呤依赖性酶可以分为芳香族氨基酸羟化酶家族-包括苯丙氨酸羟化酶，酪氨酸羟化酶和两种色氨酸羟化酶-以及三种一氧化氮合酶。我们测试了不同金属离子和金属离子螯合剂对甘油醚单加氧酶、苯丙氨酸羟化酶和一氧化氮合酶活性的影响，以阐明甘油醚单加氧酶与这两个家族的关系。1，10-菲咯啉是一种非血红素铁依赖性酶的抑制剂，能够有效地阻断甘油醚单加氧酶和苯丙氨酸羟化酶，但对诱导型一氧化氮合酶没有影响。两种四氢生物蝶呤类似物，N5-甲基四氢生物蝶呤和4-氨基四氢生物蝶呤，对甘油醚单加氧酶活性的影响与苯丙氨酸羟化酶相似。这些观察点的四氢生物蝶呤在甘油醚单加氧酶和芳香族氨基酸羟化酶的作用的密切的类比，并建议甘油醚单加氧酶可能需要一个nonheme铁催化。
Glyceryl ether monooxygenase is a tetrahydrobiopterin-dependent membrane-bound enzyme which catalyses the cleavage of lipid ethers into glycerol and the corresponding aldehyde. Despite many different characterisation and purification attempts, so far no gene and primary sequence have been assigned to this enzyme. The seven other tetrahydrobiopterin-dependent enzymes can be divided in the family of aromatic amino acid hydroxylases - comprising phenylalanine hydroxylase, tyrosine hydroxylase, and the two tryptophan hydroxylases - and into the three nitric oxide synthases. We tested the influences of different metal ions and metal ion chelators on glyceryl ether monooxygenase, phenylalanine hydroxylase, and nitric oxide synthase activity to elucidate the relationship of glyceryl ether monooxygenase to these two families. 1,10-Phenanthroline, an inhibitor of non heme iron dependent enzymes, was able to potently block glyceryl ether monooxygenase as well as phenylalanine hydroxylase but had no effect on inducible nitric oxide synthase. Two tetrahydrobiopterin analogues, N5-methyltetrahydrobiopterin and 4-aminotetrahydrobiopterin, had a similar impact on glyceryl ether monooxygenase activity as has already been shown for phenylalanine hydroxylase. These observations point to a close analogy of the role of tetrahydrobiopterin in glyceryl ether monooxygenase and in aromatic amino acid hydroxylases and suggest that glyceryl ether monooxygenase may require a nonheme iron for catalysis.