Muscle aldolase: The stress-dependent modification of catalytic and structural properties by rat muscle lysosomal cathepsin B

Stress-dependent variations in the properties of the rat muscle aldolase (d-fructose-1,6-bisphosphate d-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) have been linked to the corresponding changes in the levels of proteolytic activities in rat muscle. Whole-body X-irradiation of rat was shown to result in loss of muscle aldolase activity towards fructose 1,6-bisphosphate by 50% while fructose 1-phosphate activity remained unchanged (Pote, M.S. and Altekar, W. (1980) Ind. J. Biochem. Biophys. 17, 255–262). Incubation of muscle extract of irradiated rat with that from control rat or rabbit muscle aldolase caused similar changes in aldolase activity. The changes are attributed to the action of catheptic enzymes possessing latency characteristics and capable of using aldolase as a substrate; the time course of their increase after irradiation corresponds to that of loss in muscle aldolase activities. Exposure of rats to stress resulted in an increase in the ‘free’ proteolytic activity, and the concomitant loss of ‘bound’ activity in muscle lysosomes indicates labilization of lysosomal membrane. The observed degradation of aldolase in vivo by muscle lysosomes is shown to be due to the action of cathepsin B (EC 3.4.22.1) present in the proteolytic enzymes released into cytosol under stress. Inactivation of rabbit muscle aldolase and rat muscle aldolase by rat muscle cathepsin B is inhibited by leupeptin, antipain and iodoacetamide, but not by pepstatin. Inactivation is shown to be due to the release of C-terminal tyrosine if aldolase required for its catalytic activity. Cathepsin B acts as a rate-limiting enzyme in the degradation of aldolase. Such a proteolytic modification of aldolase in vivo could be relevant not only to the regulation of aldolase activity for glycolysis in muscle but also to the degradation of aldolase during stress conditions related to tissue damage and the maintenance of normal aldolase levels in the blood.