Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli

The pseudooligosaccharide acarbose is a potent inhibitor of amylases, gluco sidases, and cyclodextrin glycosyltransferase and is clinically used for th e treatment of so-called type II or insulin-independent diabetes. The compo und consists of an unsaturated aminocyclitol, a deoxyhexose, and a maltose, The unsaturated aminocyclitol moiety (also called valienamine) is primaril y responsible for the inhibition of glucosidases. Due to its structural sim ilarity to maltotetraose, we have investigated whether acarbose is recogniz ed as a substrate by the maltose/maltodextrin system of Escherichia coli. A carbose at millimolar concentrations specifically affected the growth of E. coli K-12 on maltose as the sole source of carbon and energy, Uptake of ra diolabeled 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 t he kinetics of acarbose binding to Lamp is asymmetric, The on-rate of acarb ose is approximately 30 times lower when the molecule enters the pore from the extracellular side than when it enters from the periplasmic side, Acarb ose could not be utilized as a carbon source since the compound alone was n ot a substrate of amylomaltase (MalQ) and was only poorly attacked by malto dextrin glucosidase (MalZ).