title: Inhibitors of pig kidney trehalase.
abstract: Trehazolin, a new trehalase inhibitor isolated from the culture broth of Micromonospora, was reported to be a highly specific inhibitor for porcine and silk worm trehalases with IC50 values of 5.5 x 10(-9) and 3.7 x 10(-9) M, respectively (O. Ando, H. Satake, K. Itoi, A. Sato, M. Nakajima, S. Takashi, H. Haruyama, Y. Ohkuma, T. Kinoshita, and R. Enokita (1991) J. Antibiot. 44, 1165-1168). We also found that trehazolin is a very powerful and quite specific inhibitor against purified pig kidney trehalase, giving an IC50 value of 1.9 x 10(-8) M. Lineweaver-Burk plots showed that this compound was a competitive inhibitor of the trehalase. However, even at concentrations of 200 micrograms/ml, trehazolin did not inhibit the rat intestinal maltase or sucrase, yeast alpha-glucosidase or almond beta-glucosidase. Validoxylamine A and validamycin A, two other trehalase inhibitors, showed potent competitive inhibition against purified pig kidney trehalase, with IC50 values of 2.4 x 10(-9) and 2.5 x 10(-4) M, respectively. On the other hand, validoxylamine A was almost inactive against rat intestinal sucrase and maltase, with some inhibition being observed at millimolar concentration. A number of other glucosidase inhibitors, such as MDL 25637, castanospermine, and deoxynojirimycin were also tested against the purified trehalase and showed reasonable inhibitory activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205.
authors.forename: S V
authors.initials: SV
authors.lastname: Kyosseva
authors.forename: Z N
authors.initials: ZN
authors.lastname: Kyossev
authors.forename: A D
authors.initials: AD
authors.lastname: Elbein
mesh_terms: D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000818:Animals; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000494:pharmacology*; D005959:Glucosidases / Q000187:drug effects; D007212:Indolizines / Q000494:pharmacology; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007421:Intestine, Small / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology*; D008969:Molecular Sequence Data; D051381:Rats; D013393:Sucrase / Q000187:drug effects; D013402:Sugar Alcohols / Q000494:pharmacology; D013552:Swine; D014198:Trehalase / Q000037:antagonists & inhibitors*; D015003:Yeasts / Q000201:enzymology; D054836:Indolizidines
chemical_list: D017485:1-Deoxynojirimycin; D004187:Disaccharides; D005959:Glucosidases; D007212:Indolizines; D007294:Inositol; D013393:Sucrase; D013402:Sugar Alcohols; D014198:Trehalase; C052772:MDL 25637; C071816:trehazolin; C052534:validoxylamine A; C037806:castanospermine; D054836:Indolizidines