Depletion method of blood plasma ascorbate
    2.
    发明授权
    Depletion method of blood plasma ascorbate 失效
    血浆抗坏血酸的消耗方法

    公开(公告)号:US06989143B1

    公开(公告)日:2006-01-24

    申请号:US10275195

    申请日:2000-05-02

    IPC分类号: A61K38/44

    摘要: Artificial modulation of ascorbate level was investigated in mice capable of de novo synthesis of ascorbate. When mice were given exogenous ascorbate or its physiological precursor, L-gulono-γ-lactone, the plasma level of ascorbate was elevated substantially but immediately returned to the basal levels. Comparably, the administration of ascorbate oxidase caused a rapid disappearance of plasma ascorbate but followed by an immediate restoration of ascorbate. These results indicate the difficulties encountered in the modulation of ascorbate level in the animal. However, the circulation life of the exogenous ascorbate oxidase in the animal was successfully extended by chemical modification with methoxypolyethylene glycol. The modified enzyme retained a full activity and exerted a remarkably prolonged depletion of plasma ascorbate compared with the native enzyme. This study suggests that the chemically modified ascorbate oxidase should find many uses in the animal studies on ascorbate since it was found to deplete plasma ascorbate even in the ascorbate-synthesizing animal in the absence of dietary control. The enzyme should prove to be useful in tumor control because there are tumor systems in mice and man amenable to the manipulation of ascorbate level.

    摘要翻译: 在能够从头合成抗坏血酸的小鼠中研究了抗坏血酸水平的人工调节。 当给予小鼠外源抗坏血酸或其生理前体L-gulono-γ-内酯时,抗坏血酸的血浆水平升高,但立即恢复到基础水平。 可比较地,抗坏血酸氧化酶的施用引起血浆抗坏血酸盐的快速消失,随后立即恢复抗坏血酸盐。 这些结果表明在动物体内抗坏血酸水平调节中遇到的困难。 然而,通过用甲氧基聚乙二醇进行化学修饰,成功地延长了动物中外源性抗坏血酸氧化酶的循环寿命。 与天然酶相比,修饰的酶保留了足够的活性并且显着延长了血浆抗坏血酸的消耗。 这项研究表明,化学修饰的抗坏血酸氧化酶应该在抗坏血酸动物研究中找到许多用途,因为即使在没有饮食控制的情况下,即使在抗坏血酸合成动物中也发现其消耗血浆抗坏血酸。 该酶应证明在肿瘤控制中是有用的,因为在小鼠中存在肿瘤系统,并且适合于抗坏血酸水平的操作。