Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli
Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli
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DOI：
10.1128/jb.181.8.2612-2619.1999
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发表时间：
1999-04-01
影响因子：
3.2
通讯作者：
Schneider, E
中科院分区：
文献类型：
--
作者：
Brunkhorst, C;Andersen, C;Schneider, E
假寡糖阿卡波糖是淀粉酶、葡糖苷酶和环糊精糖基转移酶的有效抑制剂，临床上用于治疗所谓的II型或胰岛素非依赖性糖尿病。该化合物由不饱和氨基环醇、脱氧己糖和麦芽糖组成。不饱和氨基环醇部分（也称为井冈霉烯胺）主要负责抑制葡萄糖苷酶。由于其结构相似的麦芽四糖，我们已经研究了阿卡波糖是否被识别为底物的麦芽糖/麦芽糖糊精系统的大肠杆菌。阿卡波糖在毫摩尔浓度下对大肠杆菌的生长有特异性影响。coli K-12以麦芽糖为唯一碳源和能量源时，阿卡波糖竞争性抑制对放射性标记麦芽糖的摄取，Ki值为1.1 μ M。麦芽糖培养的细胞运输放射性标记的阿卡波糖，表明该化合物被认为是一种底物。研究阿卡波糖与纯化的麦芽糖孔蛋白在黑色脂质膜中的相互作用揭示了阿卡波糖与Lamp结合的动力学是不对称的。当分子从细胞外侧进入孔时，阿卡波糖的结合速率比当其从周质侧进入时低约30倍，阿卡波糖不能用作碳源，因为单独的化合物不是淀粉麦芽糖酶（MalQ）的底物，并且仅被麦芽糖糊精葡糖苷酶（MalZ）很差地攻击。
The pseudooligosaccharide acarbose is a potent inhibitor of amylases, glucosidases, and cyclodextrin glycosyltransferase and is clinically used for the treatment of so-called type II or insulin-independent diabetes. The compound consists of an unsaturated aminocyclitol, a deoxyhexose, and a maltose, The unsaturated aminocyclitol moiety (also called valienamine) is primarily responsible for the inhibition of glucosidases. Due to its structural similarity to maltotetraose, we have investigated whether acarbose is recognized as a substrate by the maltose/maltodextrin system of Escherichia coli. Acarbose at millimolar concentrations specifically affected the growth of E. coli K-12 on maltose as the sole source of carbon and energy, Uptake of radiolabeled maltose was competitively inhibited by acarbose, with a K-i of 1.1 mu M. Maltose-grown cells transported radiolabeled acarbose, indicating that the compound is recognized as a substrate. Studying the interaction of acarbose with purified maltoporin in black lipid membranes revealed that the kinetics of acarbose binding to Lamp is asymmetric, The on-rate of acarbose is approximately 30 times lower when the molecule enters the pore from the extracellular side than when it enters from the periplasmic side, Acarbose could not be utilized as a carbon source since the compound alone was not a substrate of amylomaltase (MalQ) and was only poorly attacked by maltodextrin glucosidase (MalZ).