Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.2.13 (
aldolase
)
3,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In vivo proteolytic modification of liver
aldolase
on administration of leupeptin, a thiol proteinase inhibitor of microbial origin, is reported. When leupeptin was injected into rats, the activity of
aldolase
in the liver decreased to 40% of that in control rats. Molecular properties of
aldolase
isolated from the livers of control rats and leupeptin-treated rats indicated that a decrease of
aldolase
activity is attributable to hydrolysis of a peptide linkage(s) near the carboxyterminal of the enzyme. Injection of leupeptin also caused marked increase in the activities of free lysosomal proteinases, such as cathepsin A and cathepsin D and moderate increase of cathepsin B and cathepsin L. Increase in free activity of cathepsin A returned to the level of control rats by 12 hr after injection of leupeptin, whereas 36 hr was required for recovery of decreased
aldolase
activity. When insulin was coinjected with leupeptin, increase in the activity of free cathepsin A and decrease of activity of
aldolase
produced by the injection of leupeptin was prevented. These findings indicate that modification of
aldolase
may be due to action of a lysosomal protease(s). Incubation of the purified
aldolase
with the lysosomal fraction produced the same changes in properties of
aldolase
as those observed in vivo on injection of leupeptin. The
aldolase
inactivating proteinase in the lysosomal fraction was inhibited by PMSF and leupeptin and not by pepstatin. Purified cathepsin A (a serine proteinase), cathepsin B and cathepsin L (thiol proteinase) are potent inactivators of
aldolase
but cathepsin H and cathepsin D are not. Cathepsin A, B and L are involved in inactivation of
aldolase
in lysosomes. Endogenous thiol proteinase inhibitor which inhibits lysosomal thiol proteinases (cathepsin B, L and H) is found in the cytosol fraction of liver. The level of thiol proteinase inhibitor actually decreased to 60% of that in control rats in leupeptin-treated rats, suggesting that non-thiol proteinase cathepsin A is a major factor in inactivation of
aldolase
in lysosomes. Not only leupeptin but also other proteinase inhibitors (antipain,
E-64
-D, chloroquine) caused increase of labilization of the lysosomes and decrease in
aldolase
activity. Physiological stimuli which are known to induce the labilization of the lysosomal membrane, such as starvation and glucagon, caused slight or no significant increase of activities of free cathepsin A and D and resulted in no apparent change in
aldolase
activity.
...
PMID:Modification of rat liver fructose biphosphate aldolase by lysosomal proteinases. 705 71
