Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of serine protease, cathepsin B1, ornithine aminotransferase, and aldolase in skeletal muscles of mice with hereditary muscular dystrophy and their normal litter mates were studied. In dystrophic muscle, the specific and total activities of serine protease were much higher than in normal muscle, and the specific activities, but not the total activities, of cathepsin B1 and ornithine aminotransferase were twice those in normal muscle, and several new fragments, which are normally formed by limited proteolysis, were found in dystrophic muscle. When myofibrillar proteins of normal and dystrophic muscles were incubated with highly purified serine protease, their myosin, alpha-actinin and tropomyosin disappeared completely.
 ...
PMID:Serine protease in mice with hereditary muscular dystrophy. 62 6

The actin filament severing protein, Acanthamoeba actophorin, decreases the viscosity of actin filaments, but increases the stiffness and viscosity of mixtures of actin filaments and the crosslinking protein alpha-actinin. The explanation of this paradox is that in the presence of both the severing protein and crosslinker the actin filaments aggregate into an interlocking meshwork of bundles large enough to be visualized by light microscopy. The size of these bundles depends on the size of the containing vessel. The actin filaments in these bundles are tightly packed in some areas while in others they are more disperse. The bundles form a continuous reticulum that fills the container, since the filaments from a particular bundle may interdigitate with filaments from other bundles at points where they intersect. The same phenomena are seen when rabbit muscle aldolase rather than alpha-actinin is used as the crosslinker. We propose that actophorin promotes bundling by shortening the actin filaments enough to allow them to rotate into positions favorable for lateral interactions with each other via alpha-actinin. The network of bundles is more rigid and less thixotropic than the corresponding network of single actin filaments linked by alpha-actinin. One explanation may be that alpha-actinin (or aldolase) normally in rapid equilibria with actin filaments may become trapped between the filaments increasing the effective concentration of the crosslinker.
 ...
PMID:The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin. 175 66

Using an improved procedure, Z-protein was prepared from myofibrils of chicken breast muscle. The yield of pure Z-protein increased to 10 mg per kg of muscle. The chain weight of Z-protein was 55,000 in the presence of SDS. However, Z-protein was eluted before aldolase (Mr 158,000) in Sephacryl S-400 column chromatography, and, therefore, it appeared to exist as a tetramer in a physiological salt solution. Z-protein had at least four isopeptides whose isoelectric points ranged from pH 6.0 to 6.4. Anti-Z-protein antiserum reacted equally with these isopeptides. The extinction coefficient of Z-protein at wavelength 278 nm was 4.2 (1%; light path, 1 cm). Z-protein which was purified according to this improved method did not bind to F-actin and alpha-actinin in a physiological salt solution.
 ...
PMID:Refined purification and characterization of Z-protein. 277 42

A method is described for forming two-dimensional (2-D) paracrystalline complexes of F-actin and bundling/gelation proteins on positively charged lipid monolayers. These arrays facilitate detailed structural studies of protein interactions with F-actin by eliminating superposition effects present in 3-D bundles. Bundles of F-actin have been produced using the glycolytic enzymes aldolase and glyceraldehyde-3-phosphate dehydrogenase, the cytoskeletal protein erythrocyte adducin as well as smooth muscle alpha-actinin from chicken gizzard. All of the 2-D bundles formed contain F-actin with a 13/6 helical structure. F-actin-aldolase bundles have an interfilament spacing of 12.6 nm and a superlattice arrangement of actin filaments that can be explained by expression of a local twofold axis in the neighborhood of the aldolase. Well ordered F-actin-alpha-actinin 2-D bundles have an interfilament spacing of 36 nm and contain crosslinks 33 nm in length angled approximately 25-35 degrees to the filament axis. Images and optical diffraction patterns of these bundles suggest that they consist of parallel, unipolar arrays of actin filaments. This observation is consistent with an actin crosslinking function at adhesion plaques where actin filaments are bound to the cell membrane with uniform polarity.
 ...
PMID:Formation of two-dimensional complexes of F-actin and crosslinking proteins on lipid monolayers: demonstration of unipolar alpha-actinin-F-actin crosslinking. 785 34

In a study of myofibrillar proteins, Chowrashi and Pepe [1982: J. Cell Biol. 94:565-573] reported the isolation of a new, 85-kD Z-band protein that they named amorphin. We report that partial sequences of purified amorphin protein indicate that amorphin is identical to phosphorylase, an enzyme important in the metabolism of glycogen. Anti-amorphin antibodies also reacted with purified chicken and rabbit phosphorylase. To explore the basis for phosphorylase's (amorphin's) localization in the Z-bands of skeletal muscles, we reacted biotinylated alpha-actinin with purified amorphin and with purified phosphorylase and found that alpha-actinin bound to each. Radioimmune assays also indicated that phosphorylase (amorphin) bound to alpha-actinin, and, with lower affinity, to F-actin. Negative staining of actin filaments demonstrated that alpha-actinin mediates the binding of phosphorylase to actin filaments. There are several glycolytic enzymes that bind actin (e.g., aldolase, phosphofructokinase, and pyruvate kinase), but phosphorylase is the first one demonstrated to bind alpha-actinin. Localization of phosphorylase in live cells was assessed by transfecting cultures of quail embryonic myotubes with plasmids expressing phosphorylase fused to Green Fluorescent Protein (GFP). This resulted in targeting of the fusion protein to Z-bands accompanied by a diffuse pattern in the cytoplasm.
 ...
PMID:Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein. 1221 Nov 9

Previously we have reported that in vitro muscle aldolase binds to muscle FBPase [Biochem. Biophys. Res. Commun. 275 (2000) 611-616] which results in the changes of regulatory properties of the latter enzyme. In the present paper, the evidence that aldolase binds to FBPase in living cell is presented. The colocalization experiment, in which aldolase was diffused into skinned fibres that had been pre-incubated with FBPase, has shown that aldolase in the presence of FBPase binds predominantly to the Z-line. The existence of a triple aldolase-FBPase-alpha-actinin complex was confirmed through a real-time interaction analysis using the BIAcore biosensor. The colocalization of FBPase and aldolase on alpha-actinin of the Z-line indicates the existence of glyconeogenic metabolon in vertebrates' myocytes.
 ...
PMID:Colocalization of muscle FBPase and muscle aldolase on both sides of the Z-line. 1459 12

Fructose 1,6-bisphosphatase (FBPase) is known to form a supramolecular complex with alpha-actinin and aldolase on both sides of the Z-line in skeletal muscle cells. It has been proposed that association of aldolase with FBPase not only desensitizes muscle FBPase toward AMP inhibition but it also might enable the channeling of intermediates between the enzymes [Rakus et al. (2003) FEBS Lett. 547, 11-14]. In the present paper, we tested the possibility of fructose 1,6-bisphosphate (F1,6-P(2)) channeling between aldolase and FBPase using the approach in which an inactive form of FBPase competed with active FBPase for binding to aldolase and thus decreased the rate of aldolase-FBPase reaction. The results showed that F1,6-P(2) is transferred directly from aldolase to FBPase without mixing with the bulk phase. Further evidence that F1,6-P(2) is channeled from aldolase to FBPase comes from the experiments investigating the inhibitory effect of a high concentration of magnesium ions on aldolase-FBPase activity. FBPase in a complex with aldolase, contrary to free muscle FBPase, was not inhibited by high Mg(2+) concentrations, which suggests that free F1,6-P(2) was not present in the assay mixture during the reaction. A real-time interaction analysis between aldolase and FBPase revealed a dual role of Mg(2+) in the regulation of the aldolase-FBPase complex stability. A physiological concentration of Mg(2+) increased the affinity of muscle FBPase to muscle aldolase, whereas higher concentrations of the cation decreased the concentration of the complex. We hypothesized that the presence of Mg(2+) stabilizes a positively charged cavity within FBPase and that it might enable an interaction with aldolase. Because magnesium decreased the binding constant (K(a)) between aldolase and FBPase in a manner similar to the decrease of K(a) caused by monovalent cations, it is postulated that electrostatic attraction might be a driving force for the complex formation. It is presumed that the biological relevance of F1,6-P(2) channeling between aldolase and FBPase is protection of this glyconeogenic, as well as glycolytic, intermediate against degradation by cytosolic aldolase, which is one of the most abundant enzyme of glycolysis.
 ...
PMID:Interaction between muscle aldolase and muscle fructose 1,6-bisphosphatase results in the substrate channeling. 1555 2

In skeletal muscles, FBPase-aldolase complex is located on alpha-actinin of the Z-line. In the present paper, we show evidence that stability of the complex is regulated by calcium ions. Real time interaction analysis, confocal microscopy and the protein exchange method have revealed that elevated calcium concentration decreases association constant of FBPase-aldolase and FBPase-alpha-actinin complex, causes fast dissociation of FBPase from the Z-line and slow accumulation of aldolase within the I-band and M-line. Therefore, the release of Ca2+ during muscle contraction might result, simultaneously, in the inhibition of glyconeogenesis and in the acceleration of glycolysis.
 ...
PMID:The effect of calcium ions on subcellular localization of aldolase-FBPase complex in skeletal muscle. 1575 49

Subcellular localization of muscle FBPase-a regulatory enzyme of glyconeogenesis-was investigated in carp using immunohistochemistry and protein exchange method. Results of the experiments revealed that, in striated muscles, FBPase associates with alpha-actinin of the Z-line and co-localizes with aldolase. Additionally, in cardiac and smooth muscle cells FBPase is present inside the nuclei. In the light of findings on mammalian muscle FBPase, the data presented here indicates that interaction of the enzyme with specific cellular partners and nuclear presence of FBPase is a general phenomenon in contemporary vertebrates.
 ...
PMID:Subcellular localization of muscle FBPase in carp (Cyprinus carpio) tissues. 1658 Aug 59