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)

We have isolated and characterised the gene (PGK) encoding the glycolytic enzyme 3-phosphoglycerate kinase (PGK) from the human malaria parasite Plasmodium falciparum. This was achieved using the polymerase chain reaction (PCR) to amplify genomic DNA with primers constructed on the basis of conserved regions identified within PGK molecules of other organisms, and using the PCR product to isolate genomic clones. The gene is present in a single copy, encoding a protein of 416 amino acids (aa). The predicted aa sequence (45.5 kDa) displays approx. 60% identity to both human and yeast PGK molecules, and of the three P. falciparum glycolytic enzymes reported to date, has the greatest sequence identity to the host homologue. All aa residues implicated in substrate and cofactor binding and catalysis are conserved in the malarial PGK molecule, but there are major differences in overall composition, with implications for enzyme stability. In asexual blood-stage parasites, a single mRNA transcript of approx. 2.1 kb is observed. We have mapped the PGK gene to chromosome 9 of the parasite, and a further gene encoding a glycolytic enzyme, aldolase, to chromosome 14.
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PMID:Glycolytic pathway of the human malaria parasite Plasmodium falciparum: primary sequence analysis of the gene encoding 3-phosphoglycerate kinase and chromosomal mapping studies. 205 63

The cellular distribution of free and bound glycolytic enzymes in vivo was estimated by means of a model based on previously determined association constants for individual binding interactions and in vivo protein concentrations. The calculations revealed that a significant proportion of the enzymes would be either associated with F-actin, or bound in binary enzyme-enzyme complexes in vivo. An analysis of the relative concentration, and relative activity, of F-actin-bound enzymes suggested that a complete glycolytic complex, composed of all enzymatic steps from phosphofructokinase (PFK) to lactate dehydrogenase (LDH) does not exist. This was indicated by a very low concentration of F-actin-associated phosphoglycerate kinase (PGK) and by a very low activity of F-actin bound aldolase and PGK; this model showed that aldolase and PGK would be absent from any F-actin bound complex. An analysis of soluble enzyme-enzyme associations indicated that formation of binary enzyme complexes may lead to an increased overall flux through glyceraldehyde 3-phosphate dehydrogenase and LDH, but would serve to decrease flux through PFK and aldolase. A 1.4-fold activation of PFK, which occurs when the soluble enzyme binds to F-actin, suggested that reversible binding of PFK to F-actin may represent a novel cellular mechanism for controlling glycolytic flux during periods of increased metabolic demand by controlling the key regulatory enzyme of glycolysis.
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PMID:A quantitative evaluation of the effect of enzyme complexes on the glycolytic rate in vivo: mathematical modeling of the glycolytic complex. 206 1

The genes encoding glycolytic enzymes in Drosophila form a group of functionally related genes that may be coordinately regulated and thus controlled by common factors. We have examined the effect of dietary carbohydrates and ethanol on expression of the genes encoding glycerol-3-phosphate dehydrogenase (GPDH), aldolase (ALD), and phosphoglycerate kinase (PGK) in D. melanogaster larvae. GPDH activity and transcript abundance increased in response to ethanol and additional amounts of several different carbohydrates. In addition, the levels of two alternatively processed Gpdh transcripts were differentially regulated by the treatments. The nutritional conditions tested had little or no effect on the activities and transcript levels of ALD and PGK. These results indicate that changes in dietary conditions affect expression of specific genes and do not evoke a general response from genes involved in cellular metabolism. The observation that dietary carbohydrates and ethanol increase Gpdh expression without affecting expression of Ald and Pgk reinforces previous suggestions that dietary carbon can be diverted by GPDH from glycolytic catabolism into lipid biosynthesis.
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PMID:Effect of dietary carbohydrates and ethanol on expression of genes encoding sn-glycerol-3-phosphate dehydrogenase, aldolase, and phosphoglycerate kinase in Drosophila larvae. 212 75

Skeletal muscle triads are possessing the whole set of enzymes of the phosphatidylinositol (PI)-linked signal generating pathway, PI-kinase, PI(4)P-kinase, and PI(4,5)P2-phospholipase C (PLC). The activities of these enzymes are comparable to those found in other cell types for which a functional role of the PI-pathway in intracellular signal transduction has been established. For skeletal muscle an unequivocal function and an initiating signal for Ins(1,4,5)P3-liberation is still unknown. However, the observed Ca-dependency of PLC activity suggests that here Ins(1,4,5)P3 production is a consequence rather than a cause of increasing cytosolic Ca2+. Recently, the glycolytic enzyme aldolase, whose activity can be modulated by inositol polyphosphates, has been localized in the triadic structure. The enzyme which has a high affinity to Ins(1,4)P2, Ins(1,4,5)P3 and Ins(1,3,4,5)P4, seems to be compartmentalized to the junctional foot structure from which it is released upon binding of these molecules. This phenomenon could reflect a capability for regulation of the glycolytic flux even for aldolase, especially if a non steady-state situation in the junctional gap is considered. Meanwhile we have accumulated evidence for the operation of a partial glycolytic sequence in the junctional region established by the enzymes aldolase, glyceraldehyde-3-P (GAP) dehydrogenase and phosphoglycerate kinase. This system is able to produce ATP upon oxidation of GAP and could be, because of the inositol polyphosphate-sensing abilities of aldolase, a target for the membrane associated PI-pathway. The ATP production is however transient which indicates the coupling to an ATP hydrolyzing reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of phosphatidylinositol metabolism to glycolytic pathway in skeletal muscle membranes. 228 42

Pairwise coupled reactions of fructose-1,6-bisphosphate aldolase and sn-glycerol-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and D-glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase and sn-glycerol-3-phosphate dehydrogenase have been detected by microspectrophotometry in single crystals obtained from myogen A in the presence of polyethylene glycol. Microspectrophotometric measurements with polarized light demonstrate that the protein molecules are oriented and that NADH is bound with a definite orientation to the dehydrogenases within the crystal.
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PMID:Coupled enzymatic reactions measured in a single protein crystal from myogen A. 251 36

To investigate a possible chromosomal clustering of glycolytic enzyme genes, the complete nucleotide sequence of the 8029 bp insert of Escherichia coli DNA in the ColE1 plasmid pLC33-5 of the Clarke and Carbon collection (Clark and Carbon, 1976) was determined. Genes (pgk, fda) encoding the phosphoglycerate kinase and Class II fructose 1,6-bisphosphate aldolase, respectively, of E. coli were identified. The phosphoglycerate kinase was found to be highly homologous in primary structure to the same enzyme from eukaryotic organisms. A further large open reading frame, designated gapB, was also identified, which on the basis of sequence homology, appears to encode another glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase. This putative gene differs significantly from that (designated gapA) already identified as coding for this enzyme in E. coli and which maps elsewhere on the chromosome. The products, if any, of several other open reading frames remain to be identified.
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PMID:Identification, molecular cloning and sequence analysis of a gene cluster encoding the class II fructose 1,6-bisphosphate aldolase, 3-phosphoglycerate kinase and a putative second glyceraldehyde 3-phosphate dehydrogenase of Escherichia coli. 254 7

Interactions of the glycolytic enzymes glucose-6-phosphate isomerase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, enolase, phosphoglycerate mutase, phosphoglycerate kinase, pyruvate kinase, lactate dehydrogenase type-M, and lactate dehydrogenase type-H with tubulin and microtubules were studied. Lactate dehydrogenase type-M, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and aldolase demonstrated the greatest amount of co-pelleting with microtubules. The presence of 7% poly(ethylene glycol) increased co-pelleting of the latter four enzymes and two other enzymes, glucose-6-phosphate isomerase, and phosphoglycerate kinase with microtubules. Interactions also were characterized by fluorescence anisotropy. Since the KD values of glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase for tubulin and microtubules were all found to be between 1 and 4 microM, which is in the range of enzyme concentration in cells, these enzymes are probably bound to microtubules in vivo. These observations indicate that interactions of cytosolic proteins, such as the glycolytic enzymes, with cytoskeletal components, such as microtubules, may play a structural role in the formation of the microtrabecular lattice.
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PMID:Glycolytic enzyme interactions with tubulin and microtubules. 255 25

In the past few years, very rapid advances have been made in the field of red cell enzymopathies associated with hereditary nonspherocytic hemolytic anemia, particularly in molecular basis. Nucleotide sequence and amino acid sequence of normal human red cell enzymes have been clarified in phosphofructokinase, aldolase, triosephosphate isomerase, phosphoglycerate kinase, pyruvate kinase, diphosphoglycerate mutase, glucose 6-phosphate dehydrogenase, adenylate kinase and adenosine deaminase. Furthermore, in aldolase-, triosephosphate isomerase-, diphosphoglycerate mutase-, glucose 6-phosphate dehydrogenase-, and adenylate kinase deficiency, single nucleotide changes which cause single amino acid substitutions and finally hemolysis, have been found.
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PMID:Molecular basis of red cell enzymopathies associated with hereditary nonspherocytic hemolytic anemia. 256 Apr 52

Since the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency, erythroenzymopathies associated with hereditary hemolytic anemia have been extensively investigated. Kinetic and electrophoretic studies have shown that most erythroenzymopathies are caused by the production of a mutant enzyme. Single amino acid substitutions have been determined in G6PD and phosphoglycerate kinase variants by studies of the enzyme. Except for these two enzymes, it has been difficult to purify and to characterize the patient's enzyme because of the low protein contents in red blood cells. Recent advance in recombinant DNA technology has made possible the isolation of normal genomic DNA or cDNA for several enzymes. These results permit us to study the molecular basis of erythroenzymopathies at the nucleotide level. Single base substitutions have been identified in aldolase, triosephosphate isomerase, G6PD and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. To date, all of the enzyme-deficient variants which have been investigated are caused by point mutations. An exception is a hemolytic anemia secondary to increased adenosine deaminase (ADA) activity. Red cell ADA activity increases on the order of a hundred-fold in affected individuals. The basic abnormality appears to result from overproduction of structurally normal enzyme due to abnormal translational efficiency.
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PMID:[Pathophysiology and laboratory tests of hemolytic anemia: with special reference to erythroenzymopathies]. 269 73

The partition behaviour of six enzymes of the Calvin cycle in extracts of chloroplasts from spinach (Spinacia oleracea) between two aqueous phases has been studied by countercurrent distribution. The enzymes showed distribution patterns which indicate heterogeneity and the presence of two or three fractions of most of the enzymes. When two of the enzymes, phosphoglycerate kinase and fructose-bisphosphate aldolase, were partitioned in both purified and partially purified form, they behaved like homogeneous substances. These results indicate that countercurrent distribution of crude extracts in aqueous two-phase systems is a useful method to study protein-protein interaction.
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PMID:Studies of protein-protein interaction using countercurrent distribution in aqueous two-phase systems. Partition behaviour of six Calvin-cycle enzymes from a crude spinach (Spinacia oleracea) chloroplast extract. 273 May 89


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