There is natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) in Brazil and other parts of the world. The alkaloidal
glycosidase inhibitors
swainsonine, 2-epi-lentiginosine, and calystegines B(1),
B(2),
B(3), and C(1) have been identified as constituents of this plant.
Swainsonine is a potent inhibitor of rat
lysosomal alpha-mannosidase, with an IC(50) value of 0.02 microM, whereas calystegines B(1),
B(2), and C(1) are potent inhibitors of rat lysosomal
beta-glucosidase, with IC(50) values of 2.1, 0.75, and 0.84 microM, respectively. The action of
swainsonine results in a lysosomal storage disorder that closely mimics
alpha-mannosidosis in humans. To determine whether the toxicity of I. carnea to livestock is due to purely
swainsonine or due to a combination of effects by
swainsonine and calystegines, intracellular lysosomal
glycosidase activities in normal human lymphoblasts grown with inhibitors in the medium were examined. Incubation of lymphoblasts with 0.1 microM
swainsonine for 3 days resulted in approximately 60% reduction of
alpha-mannosidase activity. On the other hand, calystegines
B(2) and C(1) showed no inhibition of
beta-glucosidase up to 1 mM; instead inclusion of calystegines
B(2) and C(1) at 100 microM in the culture medium increased its activity by 1.5- and 1.6-fold, respectively. Calystegines
B(2) and C(1) seem to act as chemical chaperones, enhancing correct folding of the
enzyme and enabling smooth trafficking to the lysosome. The lysosomal
beta-glucosidase inhibitory calystegines seem to have little risk of inducing intoxication of livestock.