ELECTROCHEMICAL AND ENZYMATIC OXIDATION OF 5-HYDROXYTRYPTOPHAN
ELECTROCHEMICAL AND ENZYMATIC OXIDATION OF 5-HYDROXYTRYPTOPHAN
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DOI：
10.1016/0022-0728(93)85026-d
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发表时间：
1993-03-10
影响因子：
4.5
通讯作者：
DRYHURST, G
中科院分区：
文献类型：
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作者：
HUMPHRIES, KA;WRONA, MZ;DRYHURST, G
L-5-羟色氨酸（5-HTPP）是中枢神经系统中神经递质5-羟色胺（5-HT）的直接前体。在阿尔茨海默病患者的脑脊液（CSF）中检测到异常但未知的5-HTPP和5-HT氧化形式。为了提供一些线索来确定阿尔茨海默氏症CSF中5-HTPP未知氧化形式的身份，研究了该吲哚的电化学驱动和酶介导（过氧化物酶+H2 O2、血浆铜蓝蛋白+ O2、酪氨酸酶+ O2）氧化。这些氧化反应的关键中间体似乎是通过非常相似的化学途径进行的，被认为是C4中心的碳正离子（2b），它与可用的亲核试剂反应。 2b与水的反应最终导致色氨酸-4，5-二酮。2B与5-HTPP反应（离子底物二聚）得到5，5 ′-二羟基-4，4 ′-二色氨酸的非对映异构体（A和B）和在一个5-HTPP残基的C4位和另一个5-HTPP残基的C5-O位连接的另一个二聚体（J）。碳阳离子2 B也攻击二聚体A、B和J，得到一族三聚体化合物。反应产物的分离方法进行了描述，并给出了光谱信息支持建议的结构。
L-5-Hydroxytryptophan (5-HTPP) is the immediate precursor of the neurotransmitter 5-hydroxytryptamine (5-HT) in the central nervous system. Aberrant but unknown oxidized forms of 5-HTPP and 5-HT have been detected in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease. In order to provide some clues to the identities of the unknown oxidized forms of 5-HTPP in Alzheimer CSF, the electrochemically driven and enzyme-mediated (peroxidase + H2O2, ceruloplasmin + O2, tyrosinase + O2) oxidations of this indole have been studied. The key intermediate in these oxidation reactions, which appear to proceed by very similar chemical pathways, is proposed to be a C4-centered carbocation (2b) which reacts with available nucleophiles. Reaction of 2b with water ultimately leads to tryptophan-4,5-dione. Reaction of 2b with 5-HTPP (an ion-substrate dimerization) gives diastereomers of 5,5'-dihydroxy-4,4'-bi-tryptophan (A and B) and a further dimer (J) linked at the C4 position of one 5-HTPP residue and the C5-O position of the other. Carbocation 2b also attacks dimers A, B and J to give a family of trimeric compounds. Methods for the isolation of reaction products are described and spectral information supporting the proposed structures is given.