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

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Query: EC:4.1.2.13 (aldolase)
3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether the energy derived from glycolysis is functionally coupled to Ca2+ active transport in sarcoplasmic reticulum (SR), we determined whether glycolytic enzymes were associated with SR membranes and whether metabolism through these enzymes was capable of supporting 45Ca transport. Sealed right-side-out SR vesicles were isolated by step sucrose gradient from rabbit skeletal and cardiac muscle. Intravesicular 45Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca(2+)-ATPase inhibitor thapsigargin. We found that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, phosphoglycerate kinase (PGK), phosphoglyceromutase, enolase, and pyruvate kinase (PK), was associated with SR vesicles from both cardiac and skeletal muscle. Iodoacetic acid, an inhibitor of GAPDH, eliminated 45Ca transport supported by fructose-1,6-diphosphate, the substrate for aldolase, but transport was completely restored by phosphoenolpyruvate (the substrate for PK), indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and PK, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca transport fueled by exogenous ATP but had markedly less effect on 45Ca transport supported by endogenously produced ATP (via glycolysis). Similarly, at very low concentrations of ATP and ADP (10 to 50 nmol/L), ATP that was produced endogenously from ADP and phosphoenolpyruvate supported 15-fold more 45Ca transport than ATP that was supplied exogenously at the same concentration. These results are consistent with functional coupling of glycolytic ATP to Ca2+ transport and support the hypothesis that ATP generated by SR-associated glycolytic enzymes may play an important role in cellular Ca2+ homeostasis by driving the SR Ca2+ pump.
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PMID:Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport. 778 86

Glycolytic enzymes are known to be controlled by reversible binding to cytoskeleton. Our previous experiments have shown that insulin, epidermal growth factor (EGF), and Ca2+ induce a rapid and transient stimulation of binding of glycolytic enzymes to muscle cytoskeleton. We show here that platelet-derived growth factor (PDGF) exerts a similar action. Incubation of rat diaphragm muscle in the presence of PDGF resulted in rapid and transient stimulation of binding of phosphofructokinase (EC 2.7.11) and aldolase (EC 4.1.2.13) to muscle cytoskeleton. The increase in cytoskeleton-bound glycolytic enzymes induced by PDGF was prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a potent and selective inhibitor of calmodulin activity), which strongly suggests that Ca(2+)-calmodulin is involved in this effect of PDGF. Similarly, we previously found that stimulation of cytoskeleton-bound glycolytic enzymes exerted by insulin, EGF, or Ca2+, was also calmodulin mediated. The present and previous results suggest that the rapid, Ca(2+)-calmodulin-mediated increase in cytoskeleton-bound glycolytic enzymes, may be a general mechanism in the cell, in signal transduction of insulin, growth factors, and other Ca(2+)-mobilizing hormones. The accelerated cytoskeletal glycolysis will provide local ATP, which is required for the rapid cytoskeletal-membrane rearrangements following binding of growth factor or hormone to its receptor.
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PMID:Platelet-derived growth factor (PDGF) rapidly stimulates binding of glycolytic enzymes to muscle cytoskeleton, prevented by calmodulin antagonists. 785 79

A class II Zn(2+)-dependent fructose-1,6-bisphosphate (FBP)- aldolase was purified from an overproducer strain of Escherichia coli and characterized by standard biochemical techniques and 13C NMR spectroscopy. The principal finding of these studies was identification, by 13C NMR spectroscopy, of an enzyme-bound reaction intermediate, the enediol(ate) form of dihydroxyacetone phosphate (DHAP). Formation of this intermediate requires the presence of Zn2+ and is pH dependent, with increasing amounts of this tautomer appearing at alkaline pH's. This pH dependence closely parallels the pH activity profile of the enzyme, suggesting an involvement of the enediol-DHAP form in the reaction pathway. In addition to these results the following observations were made on this enzyme: (a) E. coli FBP aldolase binds and utilizes only the carbonyl forms of FBP and DHAP; (b) the function of Zn2+ in this metalloaldolase appears to be polarization of the C = O bond of DHAP; (c) activity of this enzyme is unaffected by glycolytic intermediates or nucleotide phosphates such as ATP. Although these studies provide some information about the catalytic mechanism of E. coli FBP aldolase, they do not provide an explanation for the apparent regulation of this enzyme reported in previous in vivo NMR studies. While the possibility that the enzyme is allosterically regulated cannot be excluded at this time, an interesting possibility suggested by this and other studies is that in E. coli glycolytic substrates may be channeled through a multienzyme complex.
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PMID:Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis. 787 90

The interaction of phosphofructokinase and microtubules results in mutual effects: decreases overall activity of the kinase and alters the ultrastructural organization of microtubules. Electron microscopic studies provide direct evidence for the periodical cross-bridges of microtubules by the kinase. 3-4 closely aligned tubules are connected by rows of highly periodic lateral arms about 13 nm long and 12 nm wide. The bundling activity of the enzyme seems to be specific since aldolase, which also interacts with microtubules, does not cross-link tubules, but it impedes the binding of the kinase to tubules. ATP, ADP and fructose bisphosphates inhibit the cross-bridges of microtubules by phosphofruktokinase to a different extent and concentration dependent manner. The kinase complexed with specific metabolites inducing distinct conformers does not interact with tubules. Microtubules cross-linked by the kinase became partly resistant to the depolymerizing action of vinblastine.
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PMID:Ligand-modulated cross-bridging of microtubules by phosphofructokinase. 798 May 18

The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.
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PMID:In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading. 786 5

The main pathway for the fermentation of maltose or cellobiose by the hyperthermophile Pyrococcus furiosus was investigated by in vivo NMR and by enzyme measurements. Addition of [1-13C]glucose to cell suspensions resulted in the formation of C2-labeled acetate and C3-labeled alanine. No label was recovered in CO2 or HCO3-. In the presence of [3-13C]glucose, the label ended up in the C1 atom of alanine and in HCO3- and CO2. These labeling patterns indicate that glucose is converted along an Embden-Meyerhof pathway, and they disagree with the previously proposed nonphosphorylated Entner-Doudoroff pathway (pyroglycolysis). The NMR data were supported by enzyme measurements. Hexokinase (8.7 units/mg), phosphoglucose isomerase (6.8 units/mg), phosphofructokinase (0.81 unit/mg), and aldolase (0.26 unit/mg) were present in cell-free extracts (specific activities at 90 degrees C). Remarkably, the two kinases required ADP as the phosphoryl group donor instead of ATP. No activity was found with pyrophosphate. These are the first descriptions of ADP-dependent (AMP-forming) kinases to date. Since P. furiosus is a phylogenetically ancient organism, these enzymes may represent an ancestral kind of metabolism.
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PMID:Evidence for the operation of a novel Embden-Meyerhof pathway that involves ADP-dependent kinases during sugar fermentation by Pyrococcus furiosus. 802 Dec 61

Hormonal inductions of lipogenic enzyme activities (fatty acid synthetase, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and ATP-citrate lyase) were studied in primary cultured rat hepatocytes. Insulin, triiodothyronine and dexamethasone markedly stimulated the inductions of the enzymes (particularly G6PD and ME) in the presence of pyruvate. Lactate also induced their activities. The activities of these enzymes in the presence of appropriate hormone combinations and a substrate amount of pyruvate were as high as, or higher than those in the liver of rats on high-carbohydrate, low-fat diet. The aldolase and glucokinase activities induced by these hormones were not enhanced by the addition of pyruvate. The induction by pyruvate was inhibited by actinomycin D or cycloheximide. The ATP content of rat hepatocytes was maintained without increase during culture with pyruvate for 6 days. These results indicate that the additions of pyruvate, or its metabolites to cultures of isolated hepatocytes have specific effects on the inductions of certain hepatic enzymes, possibly acting at the level of transcription. Their effects are similar to those of feeding a high-carbohydrate, low-fat diet to intact animals.
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PMID:Pyruvate stimulates hormonal induction of lipogenic enzymes in primary cultured rat hepatocytes. 821 43

Mature mitochondrial proteins (aspartate aminotransferase, malate dehydrogenase, hydroxyacyl coenzyme A dehydrogenase, creatine kinase) and cytosolic proteins (aldolase, glyceraldehyde-3-phosphate dehydrogenase) with a basic pI were found to bind to isolated mitochondria, electrostatic interactions being mainly responsible for their binding. Mitochondrial aspartate aminotransferase bound with a Kd' of 30 nM in 0.6 M sorbitol, 20 mM Hepes/KOH, pH 7.4, at 25 degrees C. Cytosolic aspartate aminotransferase and glutamate dehydrogenase (a protein located in the mitochondrial matrix) both with an acidic pI, did not bind to mitochondria. Treatment of mitochondria with proteinases did not affect the subsequent binding of imported mitochondrial proteins. Their association with both intact and proteinase-treated mitochondria resulted in a marked increase in their susceptibility toward proteinase K. In contrast, the basic cytosolic proteins tested bound only to intact mitochondria and thereby did not become more susceptible toward proteolytic attack. Treatment of mitochondria with adriamycin, a drug binding to acidic phospholipids, prevented the subsequent association of mitochondrial aspartate aminotransferase with mitochondria and the ensuing conformational labilization. Apparently, the mature moiety of imported mitochondrial proteins is partially unfolded upon interaction with the lipid component of the mitochondrial envelope. Both the binding of the mitochondrial proteins and their conformational labilization is independent of ATP and the electrochemical potential across the inner membrane.
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PMID:The mature form of imported mitochondrial proteins undergoes conformational changes upon binding to isolated mitochondria. 828 42

1. We show here that treatment of diaphragm muscle with 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, abolished the stimulatory action of insulin on binding of the glycolytic enzymes, phosphofructokinase (PFK) and aldolase, to muscle cytoskeleton. This effect was demonstrated with low concentration of DNP, which caused only a small decrease in ATP and did not affect the basic levels of cytoskeleton-bound glycolytic enzymes. 2. Higher concentrations of DNP, which induced a drastic decline in ATP content, caused a decrease in cytoskeleton-bound glycolytic enzymes and damage to myofibrils. 3. These results suggest that mitochondrial ATP is required for both the preservation of the basal levels of cytoskeleton-bound glycolytic enzymes and cell structure, as well as for the expression of the stimulatory action of insulin on glycolytic enzymes' binding to muscle cytoskeleton.
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PMID:Uncoupling of mitochondrial oxidative phosphorylation abolishes the stimulatory action of insulin on the binding of glycolytic enzymes to muscle cytoskeleton. 836 51

We report here on a novel mechanism involved in epidermal growth factor (EGF) action, which shows that EGF rapidly stimulates binding of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11), and aldolase (EC 4.1.2.13) to muscle cytoskeleton. This effect was demonstrated both in vivo, in the tibialis anterior muscle from rats injected with EGF, and in vitro, in the isolated rat diaphragm muscle incubated with EGF. The increase in cytoskeleton-bound glycolytic enzymes induced by EGF was prevented, in both the in vivo and in vitro experiments, by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a potent and selective inhibitor of calmodulin activity), which strongly suggests that Ca2+ and calmodulin are involved in this effect of EGF. Our previous findings have revealed that insulin or Ca2+ exert a similar rapid stimulation of cytoskeletal glycolysis, which is also calmodulin mediated. We now hypothesize that this may be a general mechanism of signal transduction in the cell, involving Ca(2+)-mobilizing hormones and growth factors, and supplying local ATP, in the vicinity of cytoskeleton-membrane, which is required for the rapid cytoskeletal-membrane rearrangements upon membrane-induced events.
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PMID:Stimulatory effect of epidermal growth factor on binding of glycolytic enzymes to muscles cytoskeleton and the antagonistic action of calmodulin inhibitors. 837 34


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