Aldolase lysosomes

Mammalian liver and muscle frucose bisphosphate aldolases are also very susceptible to limited proteolysis (5,53-55). Cathepsin B, cathepsin L, and papain catalyze the limited proteolysis of rabbit muscle and rat liver aldolases 50,51). In fact, decrease of aldolase activity in liver is observed during starvation 109) and after administration of lysosome-tropic agents 103). Leupeptin caused an increase in osmotic sensitivity of lysosomes and an increase in the activities of free lysosomal proteinases, such as cathepsin A and cathepsin D, and a moderate increase of cathepsin B and L, and resulted in a decrease in aldolase activity. The molecular properties of aldolase isolated from the livers of control rats and leupeptin-treated rats indicated that the decrease of aldolase activity is attributable to hydrolysis of a peptide linkage(s) near the carboxyterminal of the enzyme. However, care is necessary in determining whether proteolytic modification of enzymes... 

Inactivation of Rabbit Liver and Muscle Aldolases by Limited Proteolysis by Lysosomal Cathepsin M... 

II. Inactivation of Aldolase by Membrane-Bound Lysosomal Proteinases... 

A number of laboratories have reported the inactivation of liver aldolase by lysosomal proteinases, including not only cathepsins B and Bi (5-8), but also cathepsin L (9) and a lysosomal carboxypeptidase (8). However, the role of these lysosomal proteinases in the turnover or regulation of activity of these enzymes has remained unclear. 

Fig. 1. Inactivation of rabbit liver aldolase by lysosomal proteinases. The broad peak of activity observed with the soluble fraction is due to the presence of at least four proteinases Fru-P2ase converting enzyme (CE-II), eathepsins B and L (CE-III), and cathepsin M. Cathepsin M also catalyzes the loss of Fru-P2ase activity measured at pH 7.5 (inactivation of Fru-P2ase). Only cathepsin M and CE-II were detected in the membrane fraction. Reprinted with permission from Pontremoli et al. (19).

The rate of inactivation of rabbit liver aldolase by undisrupted lysosomes from rabbit liver is comparable to that observed with the membrane fraction prepared from the same quantity of lysosomes (Fig. 3). In each case, inactivation is partially inhibited by leupeptin (Fig. 3A and B) which completely inhibits the inactivation of liver aldolase by purified... 

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