| Izvleček: | 1,4-Dideoxy-1,4-imino-l-arabinitol (l-AB1) and 2,5-dideoxy-2,5-imino-l- mannitol (l-DMDP) are much more potent inhibitors of isomaltase than their d-enantiomers. d-Enantiomers inhibited isomaltase in a competitive manner, whereas l-enantiomers were noncompetitive inhibitors of the enzyme. Similarly d-isofagomine and l-isofagomine were competitive and noncompetitive inhibitors of human lysosomal β-d-glucosidase (β-glucocerebrosidase), with K i values of 0.016 and 5.7 μM, respectively. The multiple inhibition analysis of β-glucocerebrosidase by d-isofagomine and l-isofagomine indicated that the d-enantiomer best fits the catalysis site of β-glucocerebrosidase, while the l-enantiomer has a favorable interaction with a regulatory site other than the active site. Our recent and present results suggest that d-iminosugars are competitive inhibitors of d-glycohydrolases but their l-enantiomers are noncompetitive inhibitors. © 2004 Elsevier Ltd. All rights reserved.
|
|---|