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:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat muscle glyceraldehyde-3-phosphate dehydrogenase is one of several enzymes which have been found to undergo age-related modifications. While the amount of this enzyme in muscle tissue does not change with age, both its specific activity and affinity towards its co-enzyme are significantly reduced in the old tissue. Age-related structural changes were found to exist in the nicotinamide binding site of the enzyme and the reactions leading to the activity loss in 'old' glyceraldehyde-3-phosphate dehydrogenase were shown to involve a reversible modification of the essential cysteine-149 residue at the active site of the enzyme. The aging effects were simulated by a controlled oxidation of cys-149 in samples of 'young' glyceraldehyde-3-phosphate dehydrogenase and subsequent reduction of this residue by 2-mercaptoethanol. The enzyme modified in this way closely resembles native 'old' glyceraldehyde-3-phosphate dehydrogenase, indicating that the structural modifications in the latter enzyme are indeed introduced by a post-translational process. The mechanism for aging of glyceraldehyde-3-phosphate dehydrogenase which is proposed, based on these observations, thus assumes an oxidation of cys-149 as its first step followed by irreversible conformational changes in the enzyme molecule. The aging of glyceraldehyde-3-phosphate dehydrogenase may thus be triggered by the reduced ability of old muscle tissue to protect its constituents against oxidation.
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PMID:Age-related effects in enzyme catalysis. 636 9

The ultraviolet irradiation of the yeast D-glyceraldehyde-3-phosphate dehydrogenase carboxymethylated at the active site Cys residues, as with the rabbit muscle enzyme, led to the formation of a fluorescent NAD derivative with an emission maximum at 410 nm. Similar results were obtained with the enzyme selectively carboxymethylated at only 2 of its 4 active site Cys residues. The binding of NAD+ to both the carboxymethylated enzymes is non-cooperative or only weakly negatively cooperative when determined by NAD+ quenching of the intrinsic protein fluorescence. However, determinations of the amount of fluorescent NAD derivative formed under different NAD+ concentrations show that both the carboxymethylated enzymes appeared to bind NAD+ with positive cooperativity as in the case of the binding of NAD+ to the native apoenzyme. This seems to suggest that the spatial positioning of the nicotinamide moiety at the active site of the irradiated enzyme resembles more closely that of the nicotinamide ring in the native holoenzyme as compared to the carboxymethylated enzymes.
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PMID:The cooperative behavior of yeast D-glyceraldehyde-3-phosphate. Dehydrogenase as studied by the formation of the fluorescent NAD derivative. 650 72

We investigated in rat hearts if chronic alcohol consumption causes an enzymatic adaption of the energy-supplying metabolism and/or of the alcohol-aldehyde metabolizing system. 16 rats were pair-fed with a liquid diet for 10 weeks. Ethanol was added to this diet to amount for 35% of calories in eight rats and was isocalorically replaced by saccharose in the control group. Selected enzyme activities of the glycolysis, the glycogenolysis, the beta-oxidation of fatty acids, the citric acid cycle and the alcohol-aldehyde oxidizing system were determined in the supernatants of the homogenized hearts. The intracellular redox state was assessed by measurement of the myocardial nicotinamide coenzymes. Enzyme activities of the alcohol-aldehyde metabolizing system did not alter after chronic alcohol intake. As we found that the capacity to oxidize acetaldehyde was much higher than the ability to oxidize ethanol we must question the role of acetaldehyde in inducing alcoholic cardiomyopathy. Chronic ethanol treatment significantly increased the activity of glyceraldehyde-3-phosphate dehydrogenase and decreased the activity of glycogen phosphorylase. The impairment of the hydroxyacylCoA dehydrogenase was not significant. The other measured enzyme activities did not alter, nor the intracellular redox state. The enzymatic adaption indicates an impaired glycogenolysis, an increased glycolysis, and probably a diminished beta-oxidation of fatty acids. We expect that the measurement of the responding enzyme activities in human endomyocardial biopsies should be a good tool to further classify cardiomyopathies according to biochemical criteria.
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PMID:The effect of chronic ethanol consumption on enzyme activities of the energy-supplying metabolism and the alcohol-aldehyde oxidizing system in rat hearts. 654 83

A new method of calculation, based on a direct fitting of the protein fluorescence intensity observed upon coenzyme binding (H.-P. Lutz, unpublished results), is used to study the negative cooperative behavior of glyceraldehyde-3-phosphate dehydrogenase from sturgeon muscle. The calculation procedure simultaneously elaborates data obtained for four different protein concentrations, and it is able to compare different models by computing the minimal and critical sum of squares. Using this approach, it is shown that the induced-fit model [Koshland, D. E., Jr., Nemethy, G., & Filmer, D. (1966) Biochemistry 5,365] and the dimer of dimer model [Malhotra, O. P., & Bernhard, S. A. (1968) J. Biol. Chem. 243, 1243-1252] can both be applied for explaining the negative cooperativity observed upon coenzyme binding to sturgeon glyceraldehyde-3-phosphate dehydrogenase. In addition to the progressive modification of the binding affinity during ligand binding, different maximal fluorescence quenchings for the binding steps must be postulated; and furthermore, the binding capability decreases by decreasing the protein concentration. The fact that the induced-fit model can also be applied is rather in contradiction with the view generally accepted of a dimer of dimer structure of sturgeon glyceraldehyde-3-phosphate dehydrogenase. By use of the same approach, nicotinamide 8-bromoadenine dinucleotide is shown to bind to glyceraldehyde-3-phosphate dehydrogenase from sturgeon in a negative cooperative manner.
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PMID:Applicability of the induced-fit model to glyceraldehyde-3-phosphate dehydrogenase from sturgeon muscle. Study of the binding of oxidized nicotinamide adenine dinucleotide and nicotinamide 8-bromoadenine dinucleotide. 662 10

Thermoanaerobium brockii was shown to catabolize glucose via the Embden-Meyerhof-Parnas pathway into ethanol, acetic acid, H(2)-CO(2), and lactic acid. Radioactive tracer studies, employing specifically labeled [(14)C]glucose, demonstrated significant fermentation of (14)CO(2) from C-3 and C-4 of the substrate exclusively. All extracts contained sufficient levels of activity (expressed in micromoles per minute per milligram of protein at 40 degrees C) to assign a catabolic role for the following enzymes: glucokinase, 0.40; fructose-1,6-diphosphate aldolase, 0.23; glyceraldehyde-3-phosphate dehydrogenase, 1.73; pyruvate kinase, 0.36; lactate dehydrogenase (fructose-1,6-diphosphate activated), 0.55; pyruvate dehydrogenase (coenzyme A acetylating), 0.53; hydrogenase, 3.3; phosphotransacetylase, 0.55; acetaldehyde dehydrogenase (coenzyme A acetylating), 0.15; ethanol dehydrogenase, 1.57; and acetate kinase, 1.50. All pyridine nucleotide-linked oxidoreductases examined were specific for nicotinamide adenine dinucleotide, except ethanol dehydrogenase which displayed both nicotinamide adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-linked activities. Fermentation product balances and cell growth yields supported the glucose catabolic pathway described. Representative balanced end product yields (in moles per mole of glucose fermented) were: ethanol, 0.94; l-lactate, 0.84; acetate, 0.20; CO(2), 1.31; and H(2), 0.50. Growth yields of 16.4 g of cells per mole of glucose were demonstrated. Both growth and end product yields varied significantly in accordance with the specific medium composition and incubation time.
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PMID:Glucose fermentation pathway of Thermoanaerobium brockii. 676 5

The secondary structure of glycerol-3-phosphate dehydrogenase was predicted from its amino acid sequence. The pattern of helices and sheets within the first half of the polypeptide as well as specific marker residues were consistent with the properties of the NAD binding domain in other dehydrogenases. The second half of the sequence shows similarities with the catalytic domain of glyceraldehyde-3-phosphate dehydrogenase. The resulting two-domain structure of glycerol-3-phosphate dehydrogenase allows the correct environment for the B specificity of the nicotinamide ring and the L-glycerol 3-phosphate substrate.
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PMID:Prediction of secondary structural elements in glycerol-3-phosphate dehydrogenase by comparison with other dehydrogenases. 677 74

Histochemical staining of glyceraldehyde-3-phosphate dehydrogenase activity in fresh-frozen muscle tissue may be performed using a beta-nicotinamide adenine dinucleotide (beta-NAD) reduced-dehydrogenase tetrazolium-reductase linked reaction. The phosphate-buffered incubating medium contains glyceraldehyde-3-phosphate, beta-NAD, nitro blue tetrazolium, and edetic acid. This technique produces a fine reticular pattern of blue staining in muscle fibers. In human muscle specimens, type I fibers stain darker than type II fibers.
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PMID:Histochemical staining. Its use for detection of glyceraldehyde-3-phosphate dehydrogenase in skeletal muscle. 689 50

It is shown that the modulation in the negative cooperativity of ligand binding by another, competing ligand that binds noncooperatively is accounted for exclusively by the ligand-induced sequential model. It is therefore suggested that whenever such a phenomenon is observed it argues strongly in favor of the sequential model. The advantages and limitations of this approach are evaluated. The binding of the coenzymes NAD+ and nicotinamide-1-N6-ethenoadenine dinucleotide to rabbit muscle apo-glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating; EC 1.2.1.12] exhibits strong negative cooperativity, whereas acetylpyridine adenine dinucleotide, ATP, and ADP-ribose bind noncooperatively to the NAD+ sites. The strong abolished in the presence of acetylpyridine adenine dinucleotide and strongly weakened by ATP, ADP, and AMP, but was not affected by addition of ADP-ribose. These findings demonstrate that the negative cooperativity in coenzyme binding to this enzyme results from sequential conformational changes and exclude the pre-existent asymmetry model as a possible explanation. These results also support the view that the structure of the pyridine moiety of the coenzyme analogs plays a role in orienting the adenine moiety at the adenine subsite, therefore affecting the cooperativity in the binding of the coenzyme analog which is mediated through the adenine subsites.
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PMID:Mechanism of negative cooperativity in glyceraldehyde-3-phosphate dehydrogenase deduced from ligand competition experiments. 693 45

The interactions of rat muscle glyceraldehyde-3-phosphate dehydrogenase purified from young and old animals with NADH and with the fluorescent analogue nicotinamide 1,N6-ethenoadenine dinucleotide were investigated. While the spectra of the circular polarization of fluorescence emitted by the ethenoadenine derivative when bound to the two enzyme preparations were identical large differences were revealed between the corresponding spectra in the case of NADH. From these results it was concluded that age-related modifications occur in the nicotinamide binding sites, but not in the adenine binding sites of this enzyme. The circular polarization of fluorescence of the ethenoadenine derivative was found to depend on the stoichiometry of its complexes with the enzyme while the spectra obtained for NADH were independent of the degree of saturation of the coenzyme binding sites. These observations demonstrate that progressive structural changes occur at the adenine site as a function of coenzyme saturation. These changes may be responsible for the strong negative cooperative in coenzyme binding. The finding that only the nicotinamide binding sites are affected by age explains our previous observation that while the affinity toward coenzyme binding which depends on both adenine and nicotinamide moieties is reduced upon aging the negative cooperativity of binding is not significantly changed, since this latter property depends on the state of the adenine site only.
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PMID:Location of age-related modifications in rat muscle glyceraldehyde-3-phosphate dehydrogenase. 726 90

The binding of NAD+ and of its fluorescent analogue, nicotinamide 1,N6-ethenoadenine dinucleotide, to glyceraldehyde-3-phosphate dehydrogenase purified from the muscles of young and old rats was studied in detail. Binding of the natural coenzyme was followed both by spectrophotometric titration of the extrinsic absorption band of the enzyme-NAD+ complex and from the degree of quenching of fluorescence of the protein. Binding of the coenzyme analogue was monitored by using the large enhancement in its fluorescence upon forming the complex with the enzyme. Both dinucleotides showed strong negative cooperativity in binding to the enzyme, similar to that displayed in their association with the rabbit muscle enzyme. The enzyme purified from old rats displayed a markedly reduced affinity toward the two dinucleotides, compared with the enzyme isolated from young animals. The various dissociation constants of both dinucleotides from the enzyme from young rats were remarkably similar to the corresponding constants in the rabbit muscle enzyme. The degree of negative cooperativity (i.e., the ratio between the dissociation constants from high- and low-affinity binding sites) in the "young" and "old" enzyme forms was not very different. It was concluded from these results that while modifications in the subunits take place upon aging, the intersubunit interaction is not significantly affected. Increasing concentrations of ATP were found to cause a gradual decrease in the negative cooperativity of NAD+ binding, which completely disappeared in the presence of 5 mM ATP. The observation that all four binding sites of the old enzyme display the same affinity toward NAD+ when the negative cooperativity is removed excludes the possibility that this enzyme form is a mixture of native and inactive species. The different dissociation constants of NAD+ from young and old enzyme forms in the presence of 5 mM ATP also demonstrate the occurrence of age-related modifications in the structure of the individual subunits.
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PMID:Age-related effects in coenzyme binding patterns of rat muscle glyceraldehyde-3-phosphate dehydrogenase. 730 93


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