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 simultaneous effect of calmodulin and aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) on the concentration-dependent behaviour of muscle phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) has been analysed by means of a covalently attached fluorescent probe, gel penetration experiments, and using a kinetic approach. We found that calmodulin-induced inactivation of phosphofructokinase is suspended by addition of an equimolar amount of aldolase. This effect was attributed to an apparent competition of calmodulin and aldolase for the dimeric forms of kinase. Moreover, the direct binding of aldolase to calmodulin has also been demonstrated, which resulted in a significant decrease in the kcat value of the enzyme. The quantitative analysis of these interactions in the system phosphofructokinase-calmodulin-aldolase is presented. A possible molecular model for the modulation of phosphofructokinase action by macromolecular interactions is envisaged.
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PMID:Modulation of phosphofructokinase action by macromolecular interactions. Quantitative analysis of the phosphofructokinase-aldolase-calmodulin system. 297 56

To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.
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PMID:Aldolase C is localized in neuroendocrine cells. 304 60

The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.
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PMID:Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets. 310 51

The complete protein sequence of the human aldolase C isozyme has been determined from recombinant genomic clones. A genomic fragment of 6673 base pairs was isolated and the DNA sequence determined. Aldolase protein sequences, being highly conserved, allowed the derivation of the sequence of this isozyme by comparison of open reading frames in the genomic DNA to the protein sequence of other human aldolase enzymes. The protein sequence of the third aldolase isozyme found in vertebrates, aldolase C, completes the primary structural determination for this family of isozymes. Overall, the aldolase C isozyme shared 81% amino acid homology with aldolase A and 70% homology with aldolase B. The comparisons with other aldolase isozymes revealed several aldolase C-specific residues which could be involved in its function in the brain. The data indicated that the gene structure of aldolase C is the same as other aldolase genes in birds and mammals, having nine exons separated by eight introns, all in precisely the same positions, only the intron sizes being different. Eight of these exons contain the protein coding region comprised of 363 amino acids. The entire gene is approximately 4 kilobases.
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PMID:The complete amino acid sequence of the human aldolase C isozyme derived from genomic clones. 310 2

6-Phosphofructo-1-kinase (phosphofructokinase) (ATP:D-fructose-6-P 1-phosphotransferase, EC 2.7.1.11) can be identified in sheep heart homogenates in two forms, a soluble form and a form bound to the particulate fraction. Homogenates from immediately-dissected hearts have the enzyme in the soluble form, while those collected after a delay have the enzyme bound to the particulate fraction. Aldolase appears to show the same change in its location. Homogenization in a solution with concentrated macromolecular species (20% albumin) results in a greater association of phosphofructokinase and of aldolase to the particulate fraction in homogenates from immediately dissected hearts. Phosphofructokinase activity can be solubilized by two specific means: by high ionic strength, which is dependent upon specific salts; or by low ionic strength, which is dependent upon the presence of phosphofructokinase substrates or modifier ligands. These two means of solubilization are affected differently upon decreasing the pH below 6.9: the solubilization at low ionic strength is prevented, whereas phosphofructokinase is still solubilized by high ionic strength. Under the latter condition, the enzyme is in the inactive dimeric state, which can be activated at an alkaline pH. Myofibrils present in the particulate fraction can account for the binding of phosphofructokinase in heart homogenates. Purified myofibrils, when added to heart supernatant fluids, can bind phosphofructokinase at a slightly acidic pH. Conditions for phosphofructokinase binding to myofibrils, as well as its dissociation, follow what was observed with the binding of phosphofructokinase to the particulate fraction. At an acidic pH, and in the presence of a high concentration of ATP, phosphofructokinase exhibits low activity. However, if phosphofructokinase is assayed under these conditions while bound to myofibrils, the enzyme is activated.
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PMID:Heart 6-phosphofructo-1-kinase. Subcellular distribution and binding to myofibrils. 315 84

The molecular architecture of the rabbit skeletal muscle aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) tetramer has been determined to 2.7-A resolution. Solution of the three-dimensional structure of rabbit muscle aldolase utilized phase information from a single isomorphous Pt(CN)4(2-) derivative, which was combined with iterative-phase refinement based upon the noncrystallographic 222-fold symmetry exhibited by the tetramer subunits. The electron-density map calculated from the refined phases (mf = 0.72) was interpreted on the basis of the known amino acid sequence (363 amino acids per subunit). The molecular architecture of the aldolase subunit corresponds to a singly wound beta-barrel of the parallel alpha/beta class structures as has been observed in triose phosphate isomerase, pyruvate kinase, phosphogluconate aldolase, as well as others. Close contacts between tetramer subunits are virtually all between regions of hydrophobic residues. Contrary to other beta-barrel structures, the known active-site residues are located in the center of the beta-barrel and are accessible to substrate from the COOH side of the beta-barrel. Biochemical and crystallographic data suggest that the COOH-terminal region of aldolase covers the active-site pocket from the COOH side of the beta-barrel and mediates access to the active site. On the basis of sequence studies, active-site residues as well as residues lining the active-site pocket have been totally conserved throughout evolution. By comparison, homology in the COOH-terminal region is minimal. It is suggested that the amino acid sequence of the COOH-terminal region may be, in part, the basis for the variable specific activities aldolases exhibit toward their substrates.
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PMID:Molecular architecture of rabbit skeletal muscle aldolase at 2.7-A resolution. 347 68

A new approach is described to identify the mechanism of transfer of intermediates of consecutive reactions catalysed by two functionally related enzymes. Interactions resulting in conformational changes of the individual enzymes and/or channelling of the intermediate can be identified by comparing the rate constants of the coupled and individual reactions. Using these kinetic parameters, the relative specific radioactivity of the end product can be calculated according to the different mechanisms. The comparison of these values with the experimentally determined relative specific radioactivity enhances the sensitivity of the determination. The interaction between aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) and glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) was analysed. The data agree with the model in which channeling of the intermediate was assumed. The results suggest that glyceraldehyde 3-phosphate is functionally compartmentalised within the reconstituted enzyme system, which may be relevant under physiological conditions.
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PMID:A simple approach to identify the mechanism of intermediate transfer: enzyme system related to triose phosphate metabolism. 362 Apr 81

Steady-state kinetic measurements have shown that 8-azido-1,N6-ethenoadenosine 5'-triphosphate (8-N3-epsilon ATP) can be noncovalently bound to rabbit muscle fructose 1,6-bisphosphate aldolase with Ki = 0.075 mM at pH 8.5. This binding is purely competitive with substrate and occurs at the strong binding site for mononucleotides. Photoaffinity labeling of aldolase in the presence of 8-azido-1,N6-ethenoadenosine 5'-triphosphate results in inactivation of the enzyme. Aldolase is protected against modification in the presence of the inhibitors hexitol 1,6-bisphosphate or ATP. The labeling is saturable, and a good correlation is observed between the loss of enzymatic activity and the incorporation of 8-N3-epsilon ATP into aldolase. In addition, aldolase loses its ability to bind to phosphocellulose following modification. Digestion of labeled protein with trypsin, chymotrypsin, and cyanogen bromide revealed substantial modification of peptide 259-269. Thr-265 was identified as the residue that was covalently modified by 8-N3-epsilon ATP. On the basis of these results and other data we propose a model for the mononucleotide binding site.
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PMID:Photoaffinity labeling of rabbit muscle fructose-1,6-bisphosphate aldolase with 8-azido-1,N6-ethenoadenosine 5'-triphosphate. 365 92

A search for target proteins of inositol polyphosphates in mammalian tissues revealed that fructose 1,6-bisphosphate aldolases are potent isomer-selective binders of inositol polyphosphates. Binding was measured by tryptophan fluorescence quenching, by difference spectroscopy, and, in aldolase A, by equilibrium dialysis. Among a series of inositol phosphates containing between one and six phosphates and varying in their positions, inositol 1,4,5-trisphosphate was found to be bound strongest both by aldolase A [( L]0.5 = 0.58 microM) and aldolase B [( L]0.5 = 0.83 microM). Aldolase A showed also a strong binding of inositol tetrakisphosphate [( L]0.5 = 0.83 microM), of inositol 2,4,5-trisphosphate [( L]0.5 = 1.4 microM) and of inositol 1,3,4,5,6-pentakisphosphate [( L]0.5 = 2.0 microM); in aldolase B but not in aldolase A inositol 4,5-bisphosphate was bound as strongly as inositol 1,4,5-trisphosphate [( L]0.5 = 0.95 microM) and also inositol 2,4,5-trisphosphate was tightly bound [( L]0.5 = 1.2 microM). Both in aldolase A and B, 4 mol inositol 1,4,5-trisphosphate were bound/mol tetramer, in aldolase A a total binding of 8 mol inositol 1,4-bisphosphate/mol tetramer was evaluated. Difference spectra revealed that the binding of inositol phosphates to both isoenzymes may be associated with conformational changes. The binding of all inositol phosphates led to an inhibition of the enzyme activity. In aldolase A the inhibition was purely competitive, in aldolase B a complex cooperative type of inhibition was evident with fructose 1,6-bisphosphate as a substrate whereas with fructose 1-phosphate the inhibition also was purely competitive. Model calculations based on the in vitro data indicated a significant potential of aldolase to bind preferentially inositol 1,4,5-trisphosphate also in the presence of excess fructose 1,6-bisphosphate.
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PMID:Mammalian aldolases are isomer-selective high-affinity inositol polyphosphate binders. 378 Jul 51

Rabbit liver aldolase B (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) contains 8 SH groups/subunit and no disulfide bonds. In the native enzyme 3 SH groups/subunit are titrable with 5,5'-dithiobis(2-nitrobenzoic) acid (Nbs2), 2,2'-dithiodipyridine and N-ethylmaleimide, whereas p-mercuribenzoate is able to react with 4 thiol groups per subunit. Among the three thiol groups titrable with Nbs2, two react 'fast' with simple second-order kinetics, one reacts 'slow' and for this thiol group saturation kinetics is observed, suggesting a reversible binding of Nbs2 to the enzyme prior to covalent modification. It is shown that this binding most likely occurs via ionic interactions in the region close to the active site. The kinetic differentiation between the two 'fast' reacting groups is possible by kinetic analysis of the release of Nbs residues from the modified enzyme. Modification of all exposed SH groups of aldolase B results in 14-32% loss of enzymatic activity. The complete inactivation of liver aldolase by 1 mM p-mercuribenzoate reported previously (Waud, J.M., Feldman, E. and Schray, K.J. (1981) Arch. Biochem. Biophys. 206, 292-295) is shown to be caused by a nonspecific reaction of this reagent used in large excess. It is concluded that this isoenzyme differs from muscle aldolase in the reactivity of exposed SH groups, the mechanisms of the interaction with modifying agents and also in the effect of SH group modification on the enzymatic activity.
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PMID:The reactivity and function of cysteine residues in rabbit liver aldolase B. 379 May 75


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