Lysosomal Enzyme Precursors in Human Fibroblasts. Activation of Cathepsin D Precursor in vitro and Activity of beta-Hexosaminidase A Precursor towards Ganglioside GM2

Abstract

Precursors of cathepsin D and β-hexosaminidase were isolated from secretions of human fibroblasts and their activity was studied with natural substrates. The immunoprecipitated precursor of cathepsin D, M_r 53000, was inactive with radioactive hemoglobin as substrate. At pH 3.8–4.2 an activation of the precursor took place, which was correlated by a reduction in size to M_r 51 500. The observed cleavage of cathepsin D precursor in vitro resembles the autocatalytic activation of pepsinogen. The precursor of β-hexosaminidase A is able to cleave the natural substrate G_M2 ganglioside. This reaction, like that of the mature enzyme, depends on the presence of a protein activator, which interacts with the substrate and the enzyme.