The thiol proteinase inhibitors, Z-Phe-PheCHN2 and Z-Phe-AlaCHN2, inhibit lysosomal protein degradation in isolated rat hepatocytes.

The effects on protein metabolism of Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 were examined in isolated rat hepatocytes. The two thiol proteinase inhibitors caused a drastic reduction in the degradation of both endogenous and endocytosed (asialo-fetuin) protein. The inhibition was not additive to that of the lysosomotropic base methylamine, indicating that Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 only affect lysosomal degradation. At high concentrations (0.1-1 mM) both inhibitors reduced protein synthesis strongly. This finding indicates non-specific/toxic effects, which may limit the usefulness of the inhibitors.