Quantification of the control of carbohydrate catabolism in the tapeworm Hymenolepis diminuta

1993 ◽  
Vol 71 (7-8) ◽  
pp. 315-323 ◽  
Author(s):  
Wendy Y. Precious ◽  
John Barrett
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthase ◽  
Hymenolepis Diminuta ◽  
Rate Equations ◽  
Control Analysis ◽  
Control Coefficient ◽  
Flux Control ◽  
Flux Control Coefficients ◽  
Carbohydrate Catabolism ◽  
Control Coefficients

The elasticities for the different steps of carbohydrate catabolism in the tapeworm Hymenolepis diminuta were estimated from perturbation experiments. These data were then used to calculate flux and metabolite control coefficients. Enzyme elasticities were also calculated from the rate equations and an independent estimate of the flux control coefficients for phosphoenolpyruvate carboxykinase was made by inhibitor titration. The values obtained for the flux control coefficients for carbohydrate breakdown in H. diminuta are consistent with how the pathway is thought to be controlled in vivo. A sensitivity analysis of the flux control coefficients of the important regulatory enzymes in the pathway shows that for hexokinase, phosphofructokinase, pyruvate kinase, and phosphoenolpyruvate carboxykinase there are three or four key elasticities which have a significant effect on the coefficient. For glycogen synthase, the major factor in determining the magnitude of the flux control coefficient is the relative flux through the branch.Key words: Hymenolepis diminuta, metabolic control analysis, control coefficient, enzyme elasticity.

Control analysis of photosynthetic sucrose synthesis: assignment of elasticity coefficients and flux-control coefficients to the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase

1989 ◽  
Vol 323 (1216) ◽  
pp. 327-338 ◽  
Keyword(s):  
Sucrose Phosphate Synthase ◽  
Control Analysis ◽  
Sucrose Synthesis ◽  
Flux Control ◽  
Fructose 1,6 Bisphosphatase ◽  
Flux Control Coefficients ◽  
Sucrose Phosphate ◽  
Control Coefficients ◽  
Phosphate Synthase

The use of elasticity coefficients and flux-control coefficients in a quantitative treatment of control is discussed, with photosynthetic sucrose synthesis as an example. Experimental values for elasticities for the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase are derived from their in vitro properties, and from an analysis of the in vivo relation between fluxes and metabolite levels. An empirical factor α , describing the response of the fructose 2,6-bisphosphate regulator cycle to fructose 6-phosphate is described, and an expression is derived relating α to the elasticities of the enzymes involved in this regulator cycle. The in vivo values for elasticities and α are then used in a modified form of the connectivity theorem to estimate the flux control coefficients of the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase during rapid photosynthetic sucrose synthesis.

Flux control in the rat gastrocnemius glycogen synthesis pathway by in vivo13C/31P NMR spectroscopy

2001 ◽  
Vol 280 (4) ◽  
pp. E598-E607 ◽  
Author(s):  
J. R. Chase ◽  
D. L. Rothman ◽  
R. G. Shulman
Keyword(s):  
Glucose Transport ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Synthesis Rate ◽  
31P Nmr Spectroscopy ◽  
Control Analysis ◽  
Control Coefficient ◽  
Flux Control ◽  
Muscle Glycogen Synthesis

To determine the relative contributions of glucose transport/hexokinase, glycogen synthase (GSase), and glycolysis to the control of insulin-stimulated muscle glycogen synthesis, we combined13C and 31P NMR to quantitate the glycogen synthesis rate and glucose 6-phosphate (G-6- P) levels in rat (Sprague-Dawley) gastrocnemius muscle during hyperinsulinemia at euglycemic (E) and hyperglycemic (H) glucose concentrations under thiopental anesthesia. Flux control was calculated using metabolic control analysis. The combined control coefficient of glucose transport/hexokinase (GT/Hk) for glycogen synthesis was 1.1 ± 0.03 (direct measure) and 1.14–1.16 (calculated for a range of glycolytic fluxes), whereas the control coefficient for GSase was much lower (0.011–0.448). We also observed that the increase in in vivo [G-6- P] from E to H (0.22 ± 0.03 to 0.40 ± 0.03 mM) effects a supralinear increase in the in vitro velocity of GSase, from 14.6 to 26.1 mU · kg−1 · min−1 (1.8-fold). All measurements suggest that the majority of the flux control of muscle glycogen synthesis is at the GT/Hk step.

scholarly journals Control analysis of mammalian serine biosynthesis. Feedback inhibition on the final step

1988 ◽  
Vol 256 (1) ◽  
pp. 97-101 ◽  
Author(s):  
D A Fell ◽  
K Snell
Keyword(s):  
Feedback Inhibition ◽  
Intrinsic Value ◽  
Normal Diet ◽  
Control Analysis ◽  
Flux Control ◽  
Low Protein ◽  
Flux Control Coefficients ◽  
Flux Response ◽  
Serine Biosynthesis ◽  
Control Coefficients

The flux of serine biosynthesis in the liver of the normal rabbit, and of the rat on a low protein diet, is most sensitive to the activity of phosphoserine phosphatase (flux control coefficient up to 0.97), the last of the three enzymes in the pathway after it branches from glycolysis. The concentration of the pathway product, serine, has a strong controlling influence on the flux (response coefficient up to -0.64) through feedback inhibition at this step. The pathway is therefore controlled primarily by the demand for serine rather than the supply of the pathway precursor, 3-phosphoglycerate. Under conditions where there is a lower biosynthetic flux, the flux control coefficients of the first two enzymes of the pathway are increased, and are probably dominant in the rat on a normal diet. In rabbit liver, when ethanol is used to inhibit serine biosynthesis, control can be distributed between the three enzymes, even though the reactions catalysed by the first two remain close to equilibrium. Apart from their intrinsic value in aiding the understanding of the regulation of mammalian serine metabolism, our findings illustrate the danger of assuming that there are invariant design principles in the regulation of metabolic pathways, such as feedback control on the first step after a branch.

scholarly journals The analysis of rate limitation within enzymes: relations between flux control coefficients of rate constants and unidirectional rates, rate constants and thermodynamic parameters of single isolated enzymes

1994 ◽  
Vol 300 (1) ◽  
pp. 159-164 ◽  
Author(s):  
G C Brown ◽  
C E Cooper
Keyword(s):  
Thermodynamic Parameters ◽  
Rate Constant ◽  
Rate Constants ◽  
Enzyme Mechanism ◽  
Control Coefficient ◽  
Flux Control ◽  
Flux Control Coefficient ◽  
Flux Control Coefficients ◽  
Measuring Control ◽  
Control Coefficients

The extent to which a rate constant or step within an enzyme mechanism limits the net enzyme rate in a particular condition can be quantified as a flux control coefficient. We derive here a number of relations between the control coefficients and the unidirectional rates, rate constants, and thermodynamic parameters of the enzyme. These and other relations are used to suggest a number of methods for experimentally measuring control coefficients within enzymes.

scholarly journals Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon

1986 ◽  
Vol 237 (2) ◽  
pp. 379-389 ◽  
Author(s):  
A K Groen ◽  
C W van Roermund ◽  
R C Vervoorn ◽  
J M Tager
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Carboxylase ◽  
Adenine Nucleotide ◽  
Liver Cells ◽  
Glycolytic Enzyme ◽  
Mass Action ◽  
Control Analysis ◽  
Flux Control ◽  
Flux Control Coefficients ◽  
Control Coefficients

We have used control analysis to quantify the distribution of control in the gluconeogenic pathway in liver cells from starved rats. Lactate and pyruvate were used as gluconeogenic substrates. The flux control coefficients of the various enzymes in the gluconeogenic pathway were calculated from the elasticity coefficients of the enzymes towards their substrates and products and the fluxes through the different branches in the pathway. The elasticity coefficients were either calculated from gamma/Keq. ratios (where gamma is the mass-action ratio and Keq. is the equilibrium constant) and enzyme-kinetic data or measured experimentally. It is concluded that the gluconeogenic enzyme pyruvate carboxylase and the glycolytic enzyme pyruvate kinase play a central role in control of gluconeogenesis. If pyruvate kinase is inactive, gluconeogenic flux from lactate is largely controlled by pyruvate carboxylase. The low elasticity coefficient of pyruvate carboxylase towards its product oxaloacetate minimizes control by steps in the gluconeogenic pathway located after pyruvate carboxylase. This situation occurs when maximal gluconeogenic flux is required, i.e. in the presence of glucagon. In the absence of the hormone, when pyruvate kinase is active, control of gluconeogenesis is distributed among many steps, including pyruvate carboxylase, pyruvate kinase, fructose-1,6-bisphosphatase and also steps outside the classic gluconeogenic pathway such as the adenine-nucleotide translocator.

scholarly journals Application of electrical analogues for control analysis of simple metabolic pathways

1990 ◽  
Vol 272 (1) ◽  
pp. 65-70 ◽  
Author(s):  
A K Sen
Keyword(s):  
Metabolic Pathways ◽  
Feedback Inhibition ◽  
Current Source ◽  
Control Analysis ◽  
Analogue Circuit ◽  
Flux Control ◽  
In Series ◽  
Analogue Circuits ◽  
Flux Control Coefficients ◽  
Control Coefficients

I have used electrical analogues for calculating the Flux Control Coefficients of metabolic pathways. An analogue circuit consists of resistances that are connected in series (or parallel) with a voltage (or current) source. In constructing the analogues, each of the enzymes in the pathway is associated with a resistance whose magnitude depends on the Elasticity Coefficients of the enzymes. These circuits can be designed in a heuristic fashion directly from the configuration of the pathway, without the necessity of writing down the governing equations with the use of Summation and Connectivity Theorems. The Flux Control Coefficients of the enzymes are represented by voltages across (or currents through) the resistances and are determined by an application of Ohm's Law. Results are given for (a) a simple linear pathway without feedback or feedforward regulation, and (b) a linear pathway with feedback inhibition. The analogue circuits are also convenient for assessing the relative importance of the various enzymes in flux control, and for simplifying the structure of a given pathway.

scholarly journals Study of the flux and transition time control coefficient profiles in a metabolic system in vitro and the effect of an external stimulator

1989 ◽  
Vol 260 (3) ◽  
pp. 763-769 ◽  
Author(s):  
N V Torres ◽  
R Souto ◽  
E Meléndez-Hevia
Keyword(s):  
Transition Time ◽  
Rabbit Muscle ◽  
Control Coefficient ◽  
Metabolic System ◽  
Flux Control ◽  
Time Control ◽  
Coefficient Distribution ◽  
Flux Control Coefficients ◽  
Control Coefficients

Control of flux and transition time was investigated with a reconstructed rabbit muscle glycolytic system in vitro as an experimental model. The results show agreement with the summation property for the Flux Control Coefficients [Kacser & Burns (1973) Symp. Soc. Exp. Biol. 27, 65-104; Heinrich & Rapoport (1974) Eur. J. Biochem. 42, 89-95]. Control of flux is almost exclusively located at the hexokinase- and phosphofructokinase-catalysed steps, whereas control of transition time is distributed more evenly between the enzymes of the system. The summation value of the Transition Time Control Coefficients is near to -1, suggesting the existence of another Summation Theorem besides that already stated for Flux Control Coefficients. Finally, we study the effect of an external stimulator of the system (fructose 2,6-bisphosphate) on the Control Coefficient profiles. The effect appears to be greater on the Transition Time Control Coefficient distribution than on the Flux Control Coefficients.

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