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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)

After addition of 5 mM sulfite or nitrite to glucose-metabolizing cells of Saccharomyces cerevisiae a rapid decrease of the ATP content and an inversely proportional increase in the level of inorganic phosphate was observed. The concentration of ADP shows only small and transient changes. Cells of the yeast mutant pet 936, lacking mitochondrial F1 ATPase, after addition of 5 mM sulfite or nitrite exhibit changes in ATP, ADP and inorganic phosphate very similar to those observed in wild type cells. They key enzyme of glucose degradation, glyceraldehyde-3-phosphate dehydrogenase was previously shown to be the most sulfite- or nitrite-sensitive enzyme of the glycolytic pathway. This enzyme shows the same sensitivity to sulfite or nitrite in cells of the mutant pet 936 as in wild type cells. It is concluded that the effects of sulfite or nitrite on ATP, ADP and inorganic phosphate are the result of inhibition of glyceraldehyde-3-phosphate dehydrogenase and not of inhibition of phosphorylation processes in the mitochondria. Levels of GTP, UTP and CTP show parallel changes to ATP. This is explained by the presence of very active nucleoside monophosphate kinases which cause a rapid exchange between the nucleoside phosphates. The effects of the sudden inhibition of glucose degradation by sulfite or nitrite on levels of ATP, ADP and inorganic phosphate are discussed in terms of the theory of Lynen (1942) on compensating phosphorylation and dephosphorylation in steady state glucose metabolizing yeast.
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PMID:Analysis of the energy metabolism after incubation of Saccharomyces cerevisiae with sulfite or nitrite. 353 Jan 69

Using glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase as a linked enzyme assay for determination of free inorganic phosphate, as described by Trentham et al. (1972, Biochem. J. 126, 635-644) we have been able to monitor the time course of Pi release from F-actin following ATP hydrolysis that accompanies ATP-actin polymerization. The rate constant for Pi dissociation from Mg-F-actin is 0.006 s-1 at 25 degrees C and pH 7.8, both in the presence of 1 mM Mg and 0.1 M KCl + 1 mM Mg. This result confirms the existence of ADP-Pi-F-actin as a major intermediate in the polymerization of ATP-actin (Carlier and Pantaloni, 1986, Biochemistry 25, 7789-7792). The method is potentially useful for other enzymes hydrolyzing triphosphate nucleotides, provided that the rate of Pi release is appreciably lower than 0.1 s-1.
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PMID:Measurement of Pi dissociation from actin filaments following ATP hydrolysis using a linked enzyme assay. 356 55

In the process of defining the recruitment of fuel and pathway selection in rainbow trout fast-twitch white skeletal muscle, it was clear that the near-maximal myosin adenosinetriphosphatase activity during a 10-s sprint was supported solely by phosphocreatine hydrolysis. A conservative estimate of the ATP turnover was 188 mumol X g wet wt-1 X min-1. It was not until the rate and force of contraction decreased that the relative contribution of anaerobic glycogenolysis became increasingly important. Over a 10-min period of burst swimming at approximately 120% of maximum aerobic steady-state swimming velocity of trout determined in a Brett-type swim tunnel, fatigue was associated with the near-depletion of glycogen in white muscle. The ATP turnover supported by anaerobic glycogenolysis was 78 mumol X g wet wt-1 X min-1. The glycolytic pathway appeared functional at this time with control sites being identified at hexokinase and phosphofructokinase (PFK-1). PFK-1 did not appear to be inhibited by low muscle pH (pH 6.66). In another exercise protocol lasting 30 min, complete exhaustion was related to glycogen depletion. The sum of all glycolytic intermediates from glucose 6-phosphate to pyruvate at exhaustion decreased by a dramatic 80% compared with the 25% decrease for the 10-min fatigue swimming protocol. This large depletion of glycolytic intermediates was accompanied by an 80% fall in ATP, a 70-80% reduction in the ATP/ADP and phosphorylation potential, and a 2.5-fold increase in the NAD/NADH. Associated with these changes was a marked displacement of the phosphoglycerate kinase (PGK), and the combined glyceraldehyde-3-phosphate dehydrogenase-PGK reactions from thermodynamic equilibrium. As a general conclusion, fatigue and exhaustion should be viewed as a multicomponent biochemical process in response to low glycogen and not leveled at one particular step of the glycolytic pathway.
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PMID:Regulation of anaerobic ATP-generating pathways in trout fast-twitch skeletal muscle. 360 83

Control of oxidation is the key mechanism in the regulation of energy metabolism. In glycolysis the oxidation of glyceraldehyde-3-phosphate is controlled by DPNH, which inhibits glyceraldehyde-3-phosphate dehydrogenase. In oxidative phosphorylation the inhibition of electron flow from DPNH to oxygen, called "respiratory control," is the subject of this paper. After a discussion of the physiological significance of the "tight coupling" between phosphorylation and oxidation, studies on "loosely coupled" submitochondrial particles are reported. These particles are capable of oxidative phosphorylation in the presence of a suitable phosphate acceptor system, but in contrast to controlled, intact mitochondria they oxidize DPNH in the absence of phosphate and ADP. The addition of o-phenanthroline to submitochondrial particles gives rise to an inhibition of respiration, which is partly reversed by phosphate and ADP or by dinitrophenol. The properties of this model system of respiratory control will be described.
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PMID:On the mechanism of respiratory control. 428 26

Phosphorus-31 saturation transfer NMR techniques have been employed to measure the unidirectional Pi consumption rate by respiration competent suspensions of the yeast Saccharomyces cerevisiae while the levels of ATP, ADP, and Pi are constant. These experiments are performed by saturating the ATP gamma phosphate resonance and observing the changes in the Pi resonance intensity while the yeast are respiring on endogenous substrates. The unidirectional Pi consumption rate is 3.5 +/- mumol s-1 (g of wet cells)-1. The rate is reduced 10-fold upon addition of oligomycin (80 micrograms/ML), suggesting that at least 90% of the Pi consumption activity is due to the mitochondrial F1-F0 ATPase. We have not been able to conclusively assign the remaining 10%. When the yeast are glycolyzing anaerobically, the unidirectional Pi consumption rate was 1.0 +/- 0.2 mumol s-1 (g of wet cells)-1. At most, 80% of this is due to Pi consumption by the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase leaving a residual activity of at least 0.2 mumol s-1 (g of wet cells)-1. Thus the activity in the oligomycin-inhibited cells under respiratory conditions and the nonglycolytic activity in anaerobic cells are equal to within the experimental errors. Furthermore the unidirectional rate of Pi consumption during anaerobic glycolysis is insensitive to oligomycin. These data suggest that the mitochondrial adenosinetriphosphatase is not turning over during anaerobic glycolysis. Possible explanations for this inhibition are discussed.
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PMID:In vivo phosphorus-31 nuclear magnetic resonance saturation transfer studies of adenosinetriphosphatase kinetics in Saccharomyces cerevisiae. 621 61

We suggest that temporal oscillations of concentrations of intermediates in biochemical reaction systems may enhance the efficiency of free energy conversion (reduce dissipation) in those reactions. Experiments on glycolysis are used to estimate the Gibbs free energy changes along the glycolysis mechanism, and to postulate a construct for the glycolysis "machine" which involves: the PFK reaction as the primary oscillophor; the GAPDH reaction as a phase-shifting device; and the PK reaction with the property of intrinsic oscillatory response at resonance with the driving frequency. Analysis of a simple reaction mechanism with these postulated properties shows that the conversion of free energy from reactants to products is more efficient in an oscillatory than a steady state operation. The efficiency of free energy conversion in glycolysis from glucose + ADP to products + ATP is estimated to be increased by 5--10% due to oscillations. This may have been relevant for the evolutionary development of oscillations such as in glycolysis, especially in anaerobic cells.
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PMID:Oscillations and efficiency in glycolysis. 645 14

We present an analysis of glycolysis based on experimental findings and an interpretation based on concepts of efficiency, resonance response, and control features available in highly nonlinear reaction kinetics. We begin with a model for the glycolytic mechanism that is comprehensive, includes a large number of known activations and inhibitions of enzymes by metabolites, and couples the phosphofructokinase (PFKase) and the pyruvate kinase (PKase) reactions. The PFKase and PKase reactions and the coupling between them are modeled according to experimental information, but we do not attempt to model the glyceraldehyde-3-phosphate dehydrogenase-3-phosphoglycerate kinase reaction. We use experimental data to obtain the best estimates for the kinetic parameters and test the model by calculating the concentration variations of the intermediate metabolites. We confirm oscillatory behavior and calculate the ATP/ADP ratio and the free-energy dissipation for an extended range of the kinetic parameters as a function of the driving force for the glycolytic pathway, a measure of which is the total adenine nucleotide concentration. We find agreement of the calculated results with experimental findings except for the insufficiently represented reactions. Our model shows that the average ATP/ADP ratio is increased and the average free-energy dissipation is decreased in an oscillatory compared with a steady state mode of operation. The average values of the ATP/ADP ratio and of the free energy dissipation change abruptly past the onset of sustained oscillations.
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PMID:Oscillations and control features in glycolysis: numerical analysis of a comprehensive model. 645 92

Infusion of 2 mM ethanol into perfused liver from fed rats increased the rate of oxygen uptake concomitant with the decrease in the rate of glycolysis (lactate + pyruvate production). A linear correlation (r = 0.92) was observed between the increase in the rate of oxygen uptake and the decrease in the rate of lactate + pyruvate production determined on the whole organ by the difference between influent minus effluent concentration. Miniature oxygen electrodes (tip diameter, 50 micron) were then placed on periportal or pericentral regions of the lobule on the liver surface, and local rates of oxygen uptake were determined by stopping the flow of perfusate and monitoring the rate of decrease of oxygen concentration ('stopped-flow oxygen uptake technique'). During perfusion in the anterograde direction, ethanol infusion (2 mM) increased rates of oxygen uptake about twofold more in pericentral (15 mumol X g-1 X h-1) than in periportal (7 mumol X g-1 X h-1) regions of the liver lobule in livers from well-fed rats. In contrast, ethanol did not affect the rate of oxygen uptake significantly in either region of the liver lobule in livers from fasted rats. Glucose (30 mM) decreased oxygen concentrations initially in both regions of the liver lobule when infused into livers from fasted rats perfused in the anterograde direction. Subsequently, glucose increased the oxygen concentration in pericentral but not periportal regions of the liver lobule. This increase in regional oxygen concentration correlated temporally (r = 0.99) with increases in rates of glycolysis. The addition of ethanol in the presence of glucose reduced the rate of lactate + pyruvate production and increased the rate of oxygen uptake predominantly in pericentral regions. These data are consistent with the following interpretation. Ethanol metabolism elevates NADH in both periportal and pericentral regions of the liver lobule causing redox inhibition of glyceraldehyde-3-phosphate dehydrogenase and decreased rates of glycolytic ATP synthesis. The ADP not phosphorylated in the cytosol then moves into the mitochondrion and stimulates oxygen uptake. Since ethanol and glucose elevated oxygen uptake to a greater extent in pericentral regions of the liver lobule, it is concluded that glycolysis predominates in hepatocytes located proximal to the central vein during perfusion in the anterograde direction. When similar experiments were performed with perfusion in the retrograde direction, glycolysis was localized in periportal regions of the liver lobule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Predominance of glycolysis in pericentral regions of the liver lobule. 671 31

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 cytosolic phosphate potential was estimated in isolated rat liver parenchymal cells incubated with various gluconeogenic substrates. The value of the cytosolic [ATP]/[ADP][Pi] ratio was either estimated directly from measurements of ATP, ADP and Pi after digitonin fractionation of the cells, or calculated by the metabolite indicator method. When cells were incubated with lactate, pyruvate or alanine so that net flux through the indicator enzymes was in gluconeogenic direction, there was excellent agreement between the values obtained by the two methods over a wide range of fluxes. However, when the cells were incubated with substrates that could be converted both to glucose and to lactate so that net flux through the indicator enzymes was in the glycolytic direction, a large difference in the values of the cytosolic [ATP]/([ATP][Pi]) ratio as derived by the two methods was observed. It is concluded that the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase plus 3-phosphoglycerate kinase is out of equilibrium when flux through the reaction is the glycolytic direction, and that use of the metabolite indicator method for the calculation of the cytosolic phosphate potential under these conditions leads to erroneous values.
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PMID:An evaluation of the metabolite indicator method for determining the cytosolic phosphate potential in rat liver cells. 713 15


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