Structures and Functions of Lysosomal Thiol Proteinases and Their Endogenous Inhibitor

Abstract

This chapter discusses the structures and functions of lysosomal thiol proteinases and their endogenous inhibitor. There is a very high concentration of cathepsin L in liver, which is similar to that of cathepsin B. When lysosomes are broken during homogenization of tissues, the thiol proteinase inhibitor binds to proteinases immediately. Various proteinase inhibitors of microbial origin are useful in elucidating the importance of lysosomal thiol proteinases in protein degradation; however, these inhibitors do not distinguish between cathepsin B, cathepsin L, and other thiol proteinases. Thus, specific substrates for use in the assay of individual thiol proteinases and specific inhibitors of respective proteinases must be developed. Addition of proteinase inhibitors to cells or their injection in vivo inhibits lysosomal proteinase activities, causes formation of autophagic vacuoles, and induces synthesis of hemoglobin-hydrolyzing thiol proteinase. Various blood proteins—such as asialoproteins—are degraded in liver via processes involving receptor-mediated binding, pinocytosis, fusion with primary lysosomes, and subsequent hydrolysis in secondary lysosomes.