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Acarbose, the first example of a carbophor?

Acarbose, the first example of a carbophor?
阿卡波糖,卡波佛的第一个例子?
批准号:
12815386
负责人:
Professor Dr. Erwin Schneider
金额:
$0.0万
依托单位国家:
德国
项目类别:
Research Grants
财政年份:
2005
资助国家:
德国
项目状态:
已结题
起止时间:
2004-12-31 至 2008-12-31

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中文摘要
翻译
葡萄糖苷酶抑制剂阿卡波糖由放线菌属和链霉菌属的菌株产生,是一组不寻常的细菌次生代谢物的成员,所有这些物质都能抑制各种葡萄糖苷酶。阿卡波糖用于治疗II型糖尿病患者。放线菌会产生阿卡波糖,这是一种名为阿卡波糖同系物的混合物的一部分,根据碳源的不同,还原端和非还原端的葡萄糖残留量不同。与其作为葡萄糖苷酶抑制剂的功能不同,阿卡波糖对生产有机体的好处仍不清楚。根据最近的一项假设,阿卡波糖和相关化合物可能起到所谓的碳源作用:放线菌被认为产生阿卡波糖,以防止其自然栖息地的竞争对手利用淀粉作为碳和能源。这是通过其作为葡萄糖苷酶和调节麦芽低聚糖摄取的运输系统的有效抑制物来实现的。然后,越来越多的游离阿卡波糖可被用作摄取葡萄糖或低聚糖的受体分子,在阿卡波糖基转移酶、ACBD和/或淀粉酶AcbE/Z的作用下被转移到阿卡波糖。产生的更长的同系物被运输到细胞质中,然后葡萄糖单位将被释放并进入新陈代谢。阿卡波糖被磷酸化,然后再出口,开始一个新的碳磷循环。碳的功能尚未被详细研究,将在这一应用中进行分析。
英文摘要
The ¿¿glucosidase inhibitor acarbose, produced by strains of the genera Actinoplanes and Streptomyces, is a member of an unusual group of bacterial secondary metabolites, all of which inhibit various ¿¿glucosidases. Acarbose is used in the treatment of patients suffering from diabetes type II. Actinoplanes produces acarbose as part of a mixture of compounds called ¿acarbose homologs¿ which, depending on the carbon source, differ in the number of glucose residues at both, the reducing and the non-reducing end. Unlike its function as an inhibitor of ¿¿glucosidases, the benefits of acarbose for the producing organism are still not understood. According to a recent hypothesis acarbose and related compounds might function as so called ¿carbophors¿: Actinoplanes is thought to produce acarbose in order to prevent competitors in its natural habitat from utilizing starch as a carbon and energy source. This is achieved by its function as potent inhibitor of ¿¿glucosidases and of transport systems mediating the uptake of malto-oligosaccharides. Increasing amounts of free unbound acarbose can then be used as acceptor molecules for the uptake of glucose or oligosaccharides which are transferred to acarbose by the action of the acarviosyltransferase, AcbD and/or the ¿¿amylases AcbE/Z. The resulting longer homologs are transported into the cytoplasm where glucose units will then be released and shuttled into metabolism. Acarbose is phosphorylated and re-exported to start a new ¿carbophor cycle¿. The carbophor function has not yet been studied in detail and will be analysed in this application.
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