title: Effect of chloroquine on the activity of some lysosomal enzymes involved in ganglioside degradation.
abstract: Chronic chloroquine treatment of miniature pigs resulted in increased activity of several lysosomal enzymes of the liver and brain. The most affected enzyme was alpha-fucosidase which showed a 3-fold increase in liver (P less than 0.001) and a 2-fold increase in the brain (P less than 0.01). The increased activity of the other lysosomal enzymes was generally slightly more pronounced in the liver, in which beta-hexosaminidase, alpha-mannosidase and acid phosphatase were also significantly (P less than 0.01) increased. In contrast, chloroquine added in vitro reduced the activity of the lysosomal enzymes. Three of these, alpha-fucosidase, beta-hexosaminidase and acid phosphatase, were further investigated, and at a drug concentration of 15 mM and optimum pH for each respective enzyme, the activity was reduced to 20-30% of the initial value. Kinetic analyses revealed that this inhibition was non-competitive with regard to beta-hexosaminidase but competitive with regard to alpha-fucosidase. These results indicate that there is a multifactorial effect of chloroquine on the lysosomal enzymes, and that the inhibitory effect of alpha-fucosidase and beta-hexosaminidase might well explain the ganglioside storage found in liver and brain.
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development; D002738:Chloroquine / Q000494:pharmacology*; D005732:Gangliosides / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000254:growth & development; D008247:Lysosomes / Q000201:enzymology*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D005732:Gangliosides; D002738:Chloroquine; D006026:Glycoside Hydrolases