Inactivation of fructose-1,6-bisphosphate aldolase by cathepsin L. Stimulation by ATP.
Cathepsin L was capable of destroying rabbit muscle aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) activity towards the substrate fructose 1,6-bisphosphate. The rate of loss of activity towards this substrate was stimulated (approx. 2-fold) by physiological concentrations of ATP and to a lesser degree by GTP, CTP, UTP, ADP and cyclic AMP, while PPi and Pi decreased the rate of inactivation. Other proteinases (cathepsin B, cathepsin D, trypsin and chymotrypsin) also decreased aldolase activity toward fructose 1,6-bisphosphate more rapidly in the presence of ATP and more slowly in the presence of Pi. Cathepsin L, at higher concentrations, was capable of inactivating aldolase activity towards fructose 1-phosphate and extensively degrading the enzyme; these reactions were not affected by ATP and Pi. The thermostability of aldolase was also unaffected by these ligands. ATP and Pi had no effect on the rates of hydrolysis of other proteins (hemoglobin, bovine serum albumin, casein and azocasein) by cathepsin L. These data indicate that the effects of ATP and Pi are due to interactions of these ligands with aldolase that make the enzyme more vulnerable to limited but not extensive proteolysis; these ligands do not directly affect cathepsin L activity.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002402:Cathepsin D; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002918:Chymotrypsin / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors*; D005635:Fructosediphosphates / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011817:Rabbits; D051381:Rats
D005635:Fructosediphosphates; D000255:Adenosine Triphosphate; D002403:Cathepsins; D010450:Endopeptidases; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat; D002402:Cathepsin D; D005634:Fructose-Bisphosphate Aldolase; C029063:fructose-1,6-diphosphate