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)

The association of glycolytic enzymes with the particulate fraction of the cell was assessed in the brain of the freshwater turtle, Pseudemys scripta elegans, using three different methodologies. Each method showed that a large percentage of each of eight enzymes was bound in brain. The effect of environmental anoxia (5 or 20 h submergence in N2-bubbled water at 7 degrees C) on the distribution of enzymes between free and bound states was analyzed. All three techniques showed a significant increase in the percentages of brain aldolase and glyceraldehyde-3-phosphate dehydrogenase bound during anoxia and no change in lactate dehydrogenase or creatine kinase binding. Two methodologies also showed an increase in the percent bound during anoxia for hexokinase, phosphofructokinase, and phosphoglycerate kinase. An increased association of glycolytic enzymes with structural elements of the cell during anoxia may physically position the glycolytic pathway to facilitate coupling between this ATP-generating pathway and ATP-utilizing processes, such as membrane ion pumps.
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PMID:Subcellular enzyme binding and the regulation of glycolysis in anoxic turtle brain. 153 98

The bound fractions of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and of fructose 1,6-diphosphate aldolase (ALD) were measured in intact Taenia coli. ALD was approximately 60% bound and GAPDH was approximately 41% bound. Bound ALD activity remaining in chemically demembranated Taenia coli was similar to that in intact tissue indicating a localization to the contractile apparatus. ALD was found to be specifically bound in the demembranated preparation. Chemical demembranation resulted in almost complete loss of all GAPDH activity indicating a localization of bound GAPDH to cellular membranes.
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PMID:Localization of two glycolytic enzymes in guinea-pig taenia coli. 155 49

Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads.
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PMID:Compartmentalized ATP synthesis in skeletal muscle triads. 173 94

Recent studies have demonstrated that most glycolytic enzymes can reversibly associate to form heterogeneous enzyme-enzyme (binary) complexes in vitro. However, kinetic analysis of these complexes has shown that the individual enzymes have a varied response to complex formation: some enzymes are inhibited, some are activated and some are unaffected. In order to determine the potential role of binary complexes in regulating glycolytic flux, we have mathematically calculated enzyme distributions and activities using data from in vitro binding and kinetic studies. These calculations suggest that, overall, formation of binary complexes would lower flux through phosphofructokinase and aldolase, would increase flux through glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase, and would not affect flux through triosephosphate isomerase, phosphoglycerate kinase and pyruvate kinase. The implications of these results are discussed with respect to the effect of complex formation on overall glycolytic flux and on the flux through individual enzyme loci.
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PMID:The effect of enzyme-enzyme complexes on the overall glycolytic rate in vivo. 180 92

P. falciparum lacks a functional citric acid cycle. Unlike most tissues of the mammalian host, it is totally dependent on glycolysis for energy generation. A compound which selectively inhibits the parasite's ATP-generating machinery is therefore a potential antimalarial agent. Such a drug may interact in two ways: a) by inhibiting the activity of an enzyme or b) by disturbing the micro-organization of consecutive enzymes in a metabolic pathway. In mammalian tissues the glycolytic pathway involves the cytoskeleton as a matrix to keep phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase in an optimal sterical position for rapid substrate conversion. For instance, these three enzymes bind to the band 3 protein in erythrocytes or to actin in muscle cells. P. falciparum aldolase binds with very high affinity to the band 3 protein of human erythrocyte ghosts. However, the true in vivo site of association is believed to be actin II of P. falciparum. This actin has a sequence element which is almost identical to that of the band 3 aldolase binding site. We therefore suppose that plasmodia exploit a similar matrix organization. If true, the association of these enzymes with the cytoskeleton is a target for novel antimalarials. In contrast to all vertebrate aldolases, P. falciparum and P. berghei aldolases have two neighbouring lysine residues near the carboxy-terminus. We show here that mutagenesis of these basic residues has an effect on the catalytic constants Vmax and KM and moreover, the ability to bind to band 3 is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is Plasmodium falciparum aldolase useful for rational drug design? 182 Jul 2

A quantitative histochemical method was developed for the demonstration in rat liver of the activity of phosphofructokinase, one of the enzymes assumed to be rate-limiting for glycolysis. The procedure was based on the reduction of a tetrazolium salt as final electron acceptor and a multistep reaction using the exogenous or endogenous auxiliary enzymes aldolase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase. The highest activity was found in unfixed cryostat sections of rat liver when the incubation medium contained 17% (wt/vol) polyvinyl alcohol, 100 mmol/L Tris-maleate buffer (pH 8.4), 20 mmol/L fructose-6-phosphate, 2 mmol/L ATP, 2 mmol/L MgCl2, 5.9 mmol/L NAD+, 0.47 mmol/L 1-methoxyphenazine methosulfate, 5 mmol/L sodium azide and 5 mmol/L Nitro BT. The addition of auxiliary enzymes was not necessary to demonstrate maximum activity in rat liver. The specificity of the reaction was proven by the absence of any specific (test minus control) reaction when the incubation was performed in the presence of 25 mmol/L phosphoenolpyruvate, a competitive inhibitor of phosphofructokinase. Cytophotometric analysis revealed that linear relationships exist between the amount of specific reaction product formed and incubation time and the section thickness. The Km values for fructose-6-phosphate and the Vmax values were not significantly different in periportal and pericentral areas of livers from either normally fed or 24-hr-fasted rats. The homogeneous distribution of phosphofructokinase activity in the liver acinus is in line with biochemical findings using hepatocytes isolated from the two different areas showing that these cells contained similar amounts of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Homogeneous distribution of phosphofructokinase in the rat liver acinus: a quantitative histochemical study. 183 3

The 11.5-kDa Zn(2+)-binding protein (ZnBP) was covalently linked to Sepharose. Affinity chromatography with a cytosolic subfraction from liver resulted in purification of a predominant 38-kDa protein. In comparable experiments with brain cytosol a 39-kDa protein was enriched. The ZnBP-protein interactions were zinc-specific. Both proteins were identified as fructose-1,6-bisphosphate aldolase. Experiments with crude cytosol showed zinc-specific interaction of additional enzymes involved in carbohydrate metabolism. From liver cytosol greater than 90% of the following enzymes were specifically retained: aldolase, phosphofructokinase-1, hexokinase/glucokinase, glucose-6-phosphate dehydrogenase, glycerol-3-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and fructose-1,6-bisphosphatase. Glucose-6-phosphate isomerase, phosphoglycerate kinase, enolase, lactate dehydrogenase, and most of triosephosphate isomerase remained unbound. From L-type pyruvate kinase only the phosphorylated form seems to interact with ZnBP. Using brain cytosol hexokinase, phosphofructokinase-1, and aldolase were completely bound to the affinity column, whereas glucose-6-phosphate isomerase, phosphoglycerate kinase, enolase, lactate dehydrogenase, pyruvate kinase, and most of triose-phosphate isomerase remained unbound. The behavior of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase from this tissue could not be followed. A possible function of ZnBP in supramolecular organization of carbohydrate metabolism is proposed.
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PMID:Key enzymes of carbohydrate metabolism as targets of the 11.5-kDa Zn(2+)-binding protein (parathymosin). 183 54

The presence of glycolytic enzymes and a GLUT-1-type glucose transporter in rod and cone outer segments was determined by enzyme activity assays, glucose uptake measurements, Western blotting, and immunofluorescence microscopy. Enzyme activities of six glycolytic enzymes including hexokinase, phosphofructokinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, and lactate dehydrogenase, were found to be present in purified rod outer segment (ROS) preparations. Immunofluorescence microscopy of bovine and chicken retina sections labeled with monoclonal antibodies against glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and lactate dehydrogenase have confirmed that these enzymes are present in rod and cone outer segments and not simply contaminants from the inner segments or other cells. Rod outer segments were also found to contain glucose transport activity as detected by 3-O-[14C]methylglucose uptake and exchange. The glucose transporter had a Km of 6.3 mM and a Vmax of 0.15 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for net uptake and a Km of 29 mM and a Vmax of 1.06 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for equilibrium exchange. These Km values for net uptake and equilibrium exchange are similar to values obtained for human red blood cells and are characteristic of GLUT-1-type glucose transporter. The transport was inhibited by both cytochalasin B and phloretin. Western blot analysis and immunofluorescence microscopy using type-specific glucose transporter antibodies indicated that both rod and cone outer segment plasma membranes have a GLUT-1 glucose transporter of Mr 45K as found in red blood cells and brain microsomal membranes. Solid-phase radioimmune competitive inhibition studies indicated that rod outer segment plasma membranes contained 15% the number of glucose transporters found in human red blood cell membranes and had an estimated density of 400 glucose transporter per micron2 of plasma membrane. These studies support the view that outer segments can generate energy in the form of ATP and GTP by anaerobic glycolysis to supply at least some of the energy requirements for phototransduction and other metabolic processes.
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PMID:Glycolytic enzymes and a GLUT-1 glucose transporter in the outer segments of rod and cone photoreceptor cells. 193 98

Subpellicular microtubules isolated from Trypanosoma brucei parasites were fractionated on a phosphocellulose column, and the trypanosomal p52 microtubule-associated protein was eluted along with two other proteins of 41 and 36 kDa. These proteins were found to be the glycosomal enzymes aldolase (41 kDa) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 36 kDa) by enzyme activity, antibody cross-reaction, and N-terminal sequencing. These enzymes were coprecipitated with tubulin in the presence of taxol, and aldolase had the capacity to polymerize tubulin and crosslink microtubules. Immunolocalization of anti-aldolase and anti-GAPDH antibodies did not show an interaction between these enzymes and the subpellicular microtubules. The question whether the copurification of aldolase and the subpellicular microtubules could reflect a physiological phenomenon or may be an experimental artifact is discussed.
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PMID:The association of glycosomal enzymes and microtubules: a physiological phenomenon or an experimental artifact? 197 42

Time-resolved phosphorescence anisotropy has been used to study the rotational diffusion of eosin-labeled human erythrocyte band 3 in the presence of an enzyme bound at its cytoplasmic pole. With increasing amounts of G3PD (glyceraldehyde-3-phosphate dehydrogenase) added to ghosts, the infinite time anisotropy (r infinity) increases, and at saturating concentrations, very little decay of the anisotropy r(t) occurs at all. These phenomena are reversed by elution of the enzyme with 150 mM NaCl. Prior proteolytic removal of the N-terminal 41-kDa cytoplasmic fragment of band 3 also disenables the G3PD effect. When ghosts are stripped of their residually bound G3PD, a small reduction in the fraction of immobile band 3 is observed. Finally, titration of band 3 sites with aldolase shows effects on the r(t) qualitatively similar to those observed with G3PD. On the basis of our interpretation of the heterogenous anisotropy decay of eosin-labeled band 3 [Matayoshi, E. D., & Jovin, T. M. (1991) Biochemistry (preceding paper in this issue)], we conclude that the binding of G3PD and aldolase results in the immobilization of band 3 oligomers.
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PMID:Rotational diffusion of band 3 in erythrocyte membranes. 2. Binding of cytoplasmic enzymes. 201 12


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