Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:4.1.2.13 (
aldolase
)
3,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
When leupeptin, a thiol protease inhibitor of microbial origin, was injected into rats, the activity of fructose-1,6-bisphosphate
aldolase
(
D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase
,
EC 4.1.2.13
) in the liver decreased to about 60% of that in control rats. However, the concentration of
aldolase
protein in the liver extracts, measured with a specific antibody obtained with enzyme purified on a phosphocellulose column, remained unchanged. Injection of leupeptin also caused a marked increase in the activities of free lysosomal proteases, such as cathepsin B (EC 3.4.22.1), cathepsin L (EC 3.4.22.-), cathepsin D (EC 3.4.23.5) and
lysosomal carboxypeptidase A
in the cytosol fraction. A clear inverse relationship between
aldolase
and cathepsin B activities in the cytosol fraction was demonstrated. The possibility that the less active form of
aldolase
detected in the livers of leupeptin-treated rats was produced during homogenization was excluded by showing that the
aldolase
activity was not changed by addition of various protease inhibitors to the homogenization medium., When insulin was coinjected with leupeptin, increase in the activity of free cathepsin L 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 the action of a lysosomal protease(s). Enhanced sensitivity of lysosomes to osmotic shock was demonstrated in the livers of leupeptin-treated rats, suggesting that the lysosomal membrane is labilized by administration of leupeptin. 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.
...
PMID:Proteolytic modification of rat liver fructose-1,6-bisphosphate aldolase by administration of leupeptin in vivo. 702 Jul 65
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
The intralysosomal localization of the enzymes that catalyse inactivation of rat liver
fructose-bisphosphate aldolase
(
D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase
,
EC 4.1.2.13
) to a form with antigenic activity was demonstrated. The inactivating enzymes like all other lysosomal markers tested except acid phosphatase, were readily solubilized by hypotonic shock. The inactivating enzyme activity was inhibited by PMSF, TPCK, TLCK and leupeptin, but not by pepstatin. On partial purification of the inactivating activity from the lysosomal fraction by DEAE-Sephadex (A-50) and Sephadex G-100 column chromatographies, it was copurified with
lysosomal carboxypeptidase A
and cathepsin B (EC 3.4.22.1). Studies on its substrate specificity and sensitivity to inhibitors indicated that cathepsin B and carboxypeptidase A are responsible for almost all the
aldolase
-inactivating activity in the lysosomal fraction.
...
PMID:Properties of fructose-1,6-bisphosphate aldolase inactivating enzymes in rat liver lysosomes. 726 Jan
Protein tyrosine nitration increases in vivo as a result of oxidative stress and is elevated in numerous inflammatory-associated diseases. Mammalian fructose-1,6-bisphosphate aldolases are tyrosine nitrated in lung epithelial cells and liver, as well as in retina under different inflammatory conditions. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we now show that aldolase A is nitrated in human skin fibroblasts. To reveal the consequences of tyrosine nitration, we studied the impact of peroxynitrite on the glycolytic functions of aldolase A. A peroxynitrite concentration-dependent decrease in fructose-1,6-bisphosphate cleavage activity was observed with a concomitant increase in nitrotyrosine immunoreactivity. Both V(max) and the K(m) for fructose-1,6-bisphosphate decreased after incubation with peroxynitrite. Aldolase nitrotyrosine immunoreactivity diminished following
carboxypeptidase Y
digestion, demonstrating that tyrosine residues in the carboxyl-terminal region of
aldolase
are major targets of nitration. Aldolase A contains a carboxyl-terminal tyrosine residue, Tyr(363), that is critical for its catalytic activity. Indeed, tandem mass spectrometric analysis of trypsin-digested
aldolase
showed that Tyr(363) is the most susceptible to nitration, with a modification of Tyr(342) occurring only after nitration of Tyr(363). These tyrosine nitrations likely result in altered interactions between the carboxyl-terminal region and enzyme substrate or reaction intermediates causing the decline in activity. The results suggest that tyrosine nitration of aldolase A can contribute to an impaired cellular glycolytic activity.
...
PMID:Tyrosine nitration impairs mammalian aldolase A activity. 1497 98
