Flux Control Analysis and Stoichiometric Network Modeling

2018 ◽  
pp. 91-116
Author(s):  
Mansi El-Mansi ◽  
Gregory Stephanopoulos ◽  
Ross Carlson
Keyword(s):  
Network Modeling ◽  
Control Analysis ◽  
Flux Control

Flux Control Analysis and Stoichiometric Network Modeling

2011 ◽  
pp. 165-199
Author(s):  
E El-Mansi ◽  
Gregory Stephanopoulos ◽  
Ross Carlson
Keyword(s):  
Network Modeling ◽  
Control Analysis ◽  
Flux Control

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.

scholarly journals Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

1997 ◽  
Vol 321 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Jens NIELSEN
Keyword(s):  
Metabolic Control ◽  
Reaction Rate ◽  
Reaction Rates ◽  
Rate Function ◽  
Metabolic Control Analysis ◽  
Control Analysis ◽  
Flux Control ◽  
Biochemical Pathways ◽  
Flux Control Coefficients

Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction affinity. This parameter can often be determined from experiments in vitro. The methodology is applicable only to the analysis of simple two-step pathways, but in many cases larger pathways can be lumped into two overall conversions. In cases where this cannot be done it is necessary to apply an extension of the thermokinetic description of reaction rates to include the influence of effectors. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919–927] can be much more widely applied, although it was originally based on linearized kinetics. The methodology of determining elasticity coefficients directly from pool levels is illustrated with an analysis of the first two steps of the biosynthetic pathway of penicillin. The results compare well with previous findings based on a kinetic analysis.

Instantaneous flux control analysis for biochemical systems

1979 ◽  
Vol 76 (4) ◽  
pp. 437-452 ◽  
Author(s):  
Michael C. Kohn ◽  
Lucy M. Whitley ◽  
David Garfinkel
Keyword(s):  
Control Analysis ◽  
Flux Control ◽  
Biochemical Systems

scholarly journals Control analysis of lipid biosynthesis in tissue cultures from oil crops shows that flux control is shared between fatty acid synthesis and lipid assembly

2002 ◽  
Vol 364 (2) ◽  
pp. 393-401 ◽  
Author(s):  
Umi S. RAMLI ◽  
Darren S. BAKER ◽  
Patti A. QUANT ◽  
John L. HARWOOD
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Oil Palm ◽  
Biosynthetic Pathway ◽  
Acid Synthesis ◽  
Lipid Biosynthesis ◽  
Control Analysis ◽  
Tissue Cultures ◽  
Flux Control ◽  
Oil Crops

Top-Down (Metabolic) Control Analysis (TDCA) was used to examine, quantitatively, lipid biosynthesis in tissue cultures from two commercially important oil crops, olive (Olea europaea L.) and oil palm (Elaeis guineensis Jacq.). A conceptually simplified system was defined comprising two blocks of reactions: fatty acid synthesis (Block A) and lipid assembly (Block B), which produced and consumed, respectively, a common and unique system intermediate, cytosolic acyl-CoA. We manipulated the steady-state levels of the system intermediate by adding exogenous oleic acid and, using two independent assays, measured the effect of the addition on the system fluxes (JA and JB). These were the rate of incorporation of radioactivity: (i) through Block A from [1-14C]acetate into fatty acids and (ii) via Block B from [U-14C]glycerol into complex lipids respectively. The data showed that fatty acid formation (Block A) exerted higher control than lipid assembly (Block B) in both tissues with the following group flux control coefficients (C):(i) Oil palm: ∗CJTLBlkB = 0.64±0.05 and ∗CJTLBlkB = 0.36±0.05(ii) Olive: ∗CJTLBlkB =0.57±0.10 and ∗CJTLBlkB = 0.43±0.10where ∗C indicates the group flux control coefficient over the lipid biosynthesis flux (JTL) and the subscripts BlkA and BlkB refer to defined blocks of the system, Block A and Block B. Nevertheless, because both parts of the lipid biosynthetic pathway exert significant flux control, we suggest strongly that manipulation of single enzyme steps will not affect product yield appreciably. The present study represents the first use of TDCA to examine the overall lipid biosynthetic pathway in any tissue, and its findings are of immediate academic and economic relevance to the yield and nutritional quality of oil crops.

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.

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.

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