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 α-fucosidase which showed a 3-fold increase in liver ( P < 0.001) and a 2-fold increase in the brain ( P < 0.01). The increased activity of the other lysosomal enzymes was generally slightly more pronounced in the liver, in which β-hexosaminidase, α-mannosidase and acid phosphatase were also significantly ( P < 0.01) increased. In contrast, chloroquine added in vitro reduced the activity of the lysosomal enzymes. Three of these, α-fucosidase, β-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 β-hexosaminidase but competitive with regard to α-fucosidase. These results indicate that there is a multifactorial effect of chloroquine on the lysosomal enzymes, and that the inhibitory effect of α-fucosidase and β-hexosaminidase might well explain the ganglioside storage found in liver and brain.