I. Knuesel et al., COMPARATIVE-STUDIES OF SUIDATRESTIN, A SPECIFIC INHIBITOR OF TREHALASES, Comparative biochemistry and physiology. B. Comparative biochemistry, 120(4), 1998, pp. 639-646
Suidatrestin, isolated from a Streptomyces strain, was characterized a
s a new trehalase inhibitor. Its inhibitory potential was 7 to 50-fold
higher than that of validamycin when tested against insect, fungal an
d mammalian trehalases. The kinetic properties of suidatrestin were st
udied in vitro with trehalases from flight muscle mitochondria of the
fly, Protophormia terraenovae, from larval midgut of the moth, Spodopt
era littoralis, and from porcine kidney, as well as with maltase from
yeast. Suidatrestin was inactive on maltase but inhibited all trehalas
es with IC50 values of 0.08-0.1 mu M; Ki values ranged from 0.02 to 0.
05 mu M. The very low K-i/K-m ratios (3.9 x 10(-6)-4.9 x 10(-6)) indic
ated excellent in vitro inhibitory action of suidatrestin. When inject
ed into larvae of S. littoralis, suidatrestin required high and repeti
tive doses which lead to reversible inhibition of larval growth only.
Consecutive omission of the inhibitor even stimulated weight increase
above that of controls. Significant mortality was achieved at a rather
high dose only. Injection of a growth-inhibiting dose of suidatrestin
did not change hemolymph osmolality as a measure of sugar concentrati
on. The discrepancy between in vitro and in vivo potency of suidatrest
in may be understood once its chemical structure is fully known. (C) 1
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